Overview and Key Concepts

BICC1 (BicC family RNA-binding protein 1) is a human gene encoding the protein bicaudal-C homolog 1, an evolutionarily conserved RNA-binding protein involved in post-transcriptional gene regulation (www.frontiersin.org). BICC1 was first identified in Drosophila as the gene mutated in bicaudal fly mutants, which develop mirror-duplicated posterior structures (www.frontiersin.org). The human BICC1 protein contains three N-terminal K Homology (KH) domains – classic RNA-binding motifs – and a C-terminal sterile α-motif (SAM) domain (www.frontiersin.org). The KH domains (and adjacent KH-like regions) mediate specific binding to target mRNAs, whereas the SAM domain mediates protein–protein interactions and self-oligomerization (www.frontiersin.org). These conserved domains underlie BICC1’s role as a translational repressor that binds particular mRNA transcripts and controls their stability and translation in numerous biological contexts (www.frontiersin.org) (pmc.ncbi.nlm.nih.gov).

Molecular Function: BICC1 primarily acts as a post-transcriptional regulator of gene expression. It recognizes specific RNA sequences/structures in the 3′ untranslated regions (3′UTRs) of target mRNAs and typically represses their translation or reduces their stability (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Notably, BICC1 was shown to bind a defined 32-nucleotide stem–loop structure in the 3′UTR of Xenopus Cripto-1 (an embryonic signaling factor) – this minimal RNA element is sufficient for BICC1 binding and translational repression (pmc.ncbi.nlm.nih.gov). This finding (Sheets et al., J. Biol. Chem., 2014) was the first to identify a specific Bicc1-binding RNA motif, suggesting BICC1 targets share common structural features (pmc.ncbi.nlm.nih.gov). Consistent with an RNA silencing role, BICC1 can recruit mRNA decay and translational inhibition machinery: Drosophila Bic-C physically associates with the CCR4-NOT deadenylase complex to deadenylate bound transcripts (including its own mRNA) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), indicating that BICC1 can induce mRNA poly(A) tail shortening to inhibit translation.

Subcellular Localization: BICC1 carries out its function in the cytoplasm, where it associates with macromolecular RNA–protein granules. Endogenous BICC1 protein concentrates in discrete cytoplasmic foci that co-localize with P-body markers (e.g. GW182 and HEDLS) (pmc.ncbi.nlm.nih.gov). P-bodies are sites of mRNA storage, decay, and microRNA-mediated silencing, suggesting BICC1 functions within these structures to tether and regulate target mRNAs (pmc.ncbi.nlm.nih.gov). The SAM domain is critical for this localization: it self-polymerizes and drives BICC1 oligomerization, leading to formation of BICC1 puncta in cells (pmc.ncbi.nlm.nih.gov). In vitro, the isolated human BICC1 SAM domain can assemble into a helical polymer (observed by electron microscopy) (pmc.ncbi.nlm.nih.gov). Polymerization of BICC1 via SAM is functionally important – it increases BICC1’s local concentration and forms a silencing platform for bound mRNAs (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Mutations that disrupt SAM–SAM interaction prevent BICC1 clustering and impair its ability to repress target mRNA expression (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). For example, engineered BICC1 mutants with a defective SAM interface show diffuse cytosolic distribution and fail to efficiently silence a reporter mRNA, underscoring that multimerization is required for full repressive activity (pmc.ncbi.nlm.nih.gov). Polymerization also stabilizes the BICC1 protein itself: oligomerization-deficient BICC1 is more rapidly degraded, reducing its steady-state levels (pmc.ncbi.nlm.nih.gov).

KH Domains and RNA Binding: BICC1’s three KH domains enable it to bind RNA with sequence/structure specificity. Canonical KH domains recognize short nucleotide motifs, often polypyrimidine tracts, but in BICC1 the recognition appears to involve RNA secondary structure (pmc.ncbi.nlm.nih.gov) (www.frontiersin.org). In Xenopus, the Bicc1 protein (also called Bic-C) was found to selectively bind 63 mRNA targets in early embryos (identified by RIP-seq) (www.frontiersin.org). Validated targets include cripto1 and dand5 (key regulators of Nodal/TGF-β signaling), wnt11b (a Wnt ligand), and gdf3 (a TGF-β family factor) (www.frontiersin.org) (www.frontiersin.org). These mRNAs share Bicc1-dependent repression via their 3′UTRs, and many contain predicted stem–loop elements, consistent with BICC1’s binding preferences (www.frontiersin.org) (pmc.ncbi.nlm.nih.gov). Biochemical analyses (EMSA and footprinting) confirm that BICC1’s N-terminal half (containing the KH/KHL domains) directly binds RNA hairpins – for instance, BICC1 protects the Cripto-1 3′UTR stem-loop from RNase cleavage, highlighting a direct RNA–protein interaction (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Thus, BICC1 acts by physically binding target mRNA 3′UTRs via its KH domains and forming repressive mRNP complexes.

Biological Roles and Mechanisms

Developmental and Cellular Functions

Embryonic Development: BICC1 is crucial for proper embryonic patterning and cell-fate decisions. Originally discovered through its role in fly oogenesis, Bicaudal-C was shown to repress translation of oskar mRNA at the anterior of the oocyte – Bic-C mutants had ectopic Oskar protein, causing anterior abdomen duplication (pmc.ncbi.nlm.nih.gov). In vertebrates, BICC1 performs analogous functions to spatially regulate developmental signals. Xenopus Bicc1 is a maternal determinant that localizes specific mRNAs to vegetal cells and silences them until the correct stage (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). For example, Xenopus Bicc1 restricts Cripto-1 translation to the embryo’s animal pole; without Bicc1, Cripto-1 (a co-receptor for Nodal signals) is expressed ectopically in vegetal cells, disrupting germ layer patterning (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In line with these findings, loss of BICC1 function leads to dramatic developmental defects. Mouse Bicc1 knockout or spontaneous mutants (such as jcpk and bpk alleles) exhibit left–right patterning defects – the visceral organs show random laterality due to disrupted embryonic node signaling (pmc.ncbi.nlm.nih.gov). This is attributed to misregulation of molecular cues at the embryonic node, where BICC1 is needed for planar cell polarity and proper orientation of motile cilia (pmc.ncbi.nlm.nih.gov). Indeed, Bicc1 was recently shown to bind and regulate the mRNA of Dand5 (an inhibitor of Nodal signaling crucial for left-right asymmetry), linking BICC1 to left–right axis specification (www.frontiersin.org).

Molecular Pathways: BICC1 interfaces with major signaling pathways during development. Wnt/β-catenin signaling is one pathway influenced by BICC1. In mouse embryos, loss of Bicc1 causes ectopic Wnt/β-catenin activity during gastrulation and left–right patterning (pmc.ncbi.nlm.nih.gov). Mechanistically, BICC1 helps restrain Wnt signaling by targeting key components of the pathway. A study by Rothé et al. (2015) showed that BICC1 normally inhibits Dishevelled-2 (DVL2), a central Wnt signal transducer: BICC1 binds the Dvl2 mRNA or interacts with DVL2 protein complexes, and when BICC1 polymerization is disrupted, DVL2 levels and Wnt activity rise abnormally (pmc.ncbi.nlm.nih.gov). In Xenopus, Bicc1 also binds wnt11b mRNA (encoding a noncanonical Wnt ligand) and the TGF-β ligand gdf3, ensuring these signals are produced only at the correct time and place (www.frontiersin.org). Nodal/TGF-β signaling is another pathway regulated by BICC1 through targets like Cripto-1 and Dand5, as noted above. By modulating these pathways, BICC1 has broad effects on cell fate determination, anterior–posterior and dorsal–ventral patterning, and organogenesis in the embryo (pmc.ncbi.nlm.nih.gov) (www.frontiersin.org).

Protein Family and Evolution: BICC1 belongs to the Bic-C family of RNA-binding proteins, which are found in many metazoans (www.frontiersin.org). Vertebrates typically have a single BICC1 gene (in contrast, Drosophila has a single Bic-C, and C. elegans has multiple related proteins). The sequence and domain architecture are highly conserved from fruit flies to humans (www.frontiersin.org) (www.frontiersin.org). This conservation suggests that insights from model organisms translate to human BICC1’s function. For instance, the KH3 domain and SAM domain show especially high conservation, implying they mediate critical interactions (RNA-binding and self-assembly, respectively) that have been maintained through evolution (www.frontiersin.org). Experimental evidence supports this: human BICC1 can functionally substitute for Xenopus Bicc1 in certain assays (pmc.ncbi.nlm.nih.gov), and many mRNA targets (e.g., Polycystin-2, see below) are regulated by BICC1 across species (pmc.ncbi.nlm.nih.gov) (www.frontiersin.org). Thus, BICC1 is a fundamental post-transcriptional regulator, with a role in balancing developmental signaling networks in diverse animals.

Role in Kidney Function and Cystic Disease

One of the most prominent roles of BICC1 in mammals is in kidney development and homeostasis. Multiple lines of evidence demonstrate that BICC1 is required for maintaining normal kidney architecture (www.frontiersin.org). Mice with inactivated Bicc1 display severe polycystic kidney disease (PKD)-like phenotypes: their kidneys are enlarged and full of fluid-filled cysts formed from dilated renal tubules (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These cystic kidneys closely resemble human autosomal polycystic kidney disease, indicating BICC1 is a crucial cyst suppressor in vertebrates (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Indeed, BICC1 mutations in humans have been linked to renal cystic dysplasia. Kraus et al. (2012, Human Mutation) reported two human families where recessive BICC1 loss-of-function mutations led to congenital cystic kidney disease; patient tissues showed inappropriate activation of Wnt signaling, consistent with the mouse model (pmc.ncbi.nlm.nih.gov). More recently (2022), BICC1 variants have been identified by exome sequencing in fetuses with severe cystic kidney malformations (multicystic dysplastic kidneys), further supporting its clinical relevance in kidney development (www.frontiersin.org).

Molecular function in kidney: BICC1 safeguards kidney tubule morphology by regulating specific mRNAs tied to epithelial differentiation and signaling. A key target is PKD2 (Polycystin-2), a Ca²⁺-permeable channel essential for renal tubule integrity. Wessely and colleagues (2010, published in Development) discovered that BICC1 binds to and stabilizes Pkd2 mRNA, enhancing Polycystin-2 expression (pmc.ncbi.nlm.nih.gov). In Bicc1-deficient mouse kidneys, Pkd2 levels are greatly reduced, whereas restoring Pkd2 expression can rescue some defects (pmc.ncbi.nlm.nih.gov). BICC1 regulates Pkd2 via a microRNA-dependent mechanism: the Pkd2 3′UTR contains a binding site for the microRNA miR-17, which normally represses Pkd2. BICC1 was shown to antagonize miR-17 activity on this 3′UTR (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In cells, BICC1 binding counteracts miR-17–mediated translational inhibition, resulting in higher Pkd2 protein output (pmc.ncbi.nlm.nih.gov). Consistently, in Xenopus embryos Bicc1 knockdown caused pronephric (embryonic kidney) cysts that could be rescued by inhibiting miR-17, indicating Bicc1 and miR-17 converge on Pkd2 regulation (pmc.ncbi.nlm.nih.gov). This “relief of repression” model is somewhat unique, as BICC1 in this context acts to promote a target’s expression by blocking a microRNA. It highlights that BICC1 can either repress or de-repress targets depending on the interplay with other regulators.

Beyond Pkd2, BICC1 broadly modulates the cAMP signaling pathway in kidney epithelia – a pathway central to cystogenesis. Cystic growth is fueled by elevated cyclic AMP (cAMP) levels driving proliferation and fluid secretion in tubule cells. Normally, BICC1 helps keep cAMP in check by repressing mRNAs that would otherwise raise cAMP production. Notably, BICC1 binds and downregulates the mRNA encoding adenylate cyclase 6 (ADCY6), a major cAMP-producing enzyme (pmc.ncbi.nlm.nih.gov) (www.frontiersin.org). In Bicc1-null mouse kidneys, ADCY6 protein is upregulated due to loss of BICC1-mediated silencing, leading to excess cAMP signaling (pmc.ncbi.nlm.nih.gov). BICC1 was also found to bind mRNA for PKA inhibitor-α (PKIα), a feedback regulator of Protein Kinase A (PKA) (www.frontiersin.org). Paradoxically, silencing PKIα would tend to increase PKA activity, but in context this may fine-tune cAMP pathway dynamics. The net effect of BICC1 loss is a pathogenic increase in cAMP/PKA activity in kidney cells (pmc.ncbi.nlm.nih.gov) (www.frontiersin.org). This excess cAMP promotes cyst formation – a hallmark of polycystic kidney disease. In support of this, Bicc1 mutant mice show aberrant PKA-driven cell proliferation in renal tubules and misregulated epithelial cell adhesion (disrupted E-cadherin at cell junctions) (www.nature.com), consistent with a cAMP/PKA-mediated cystic phenotype. Combining these findings, researchers in 2012 proposed that BICC1 normally functions downstream of Dicer (miRNA processor) to bring together target mRNAs and the Ago2 microRNA-silencing complex (www.frontiersin.org) (www.frontiersin.org). In the kidney, this means BICC1 cooperates with microRNAs to ensure proper post-transcriptional silencing of cAMP-promoting genes; without BICC1, that silencing is lifted, explaining cystic kidney pathology as a consequence of microRNA pathway dysregulation (pmc.ncbi.nlm.nih.gov).

Summary of BICC1 in kidney: BICC1 maintains renal tubule integrity by (1) upregulating Polycystin-2 (a cyst-preventing factor) via miR-17 antagonism, and (2) downregulating cAMP stimulatory proteins (like AC6) via microRNA-mediated silencing (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These actions place BICC1 as a pivotal node connecting ciliary signaling (polycystins), microRNA pathways, and epithelial cyclic AMP homeostasis. Its importance is underscored by the polycystic disease that results from BICC1 dysfunction in both animals and humans (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Recent Developments (2023–2024)

Research in the past two years has uncovered new roles for BICC1, especially in disease contexts like cancer, and has provided deeper molecular insights. Below are key recent findings and expert analyses:

BICC1 in Cancer and Disease: Although historically studied in developmental biology, BICC1 has emerged as a significant player in cancer biology in recent studies (2021–2023). For example, BICC1 has been implicated in pancreatic cancer aggressiveness. Huang et al. (2023, Signal Transduct. Target. Ther.) identified BICC1 as one of the top upregulated genes in pancreatic ductal adenocarcinoma associated with angiogenesis (pmc.ncbi.nlm.nih.gov). Their analysis of patient datasets showed BICC1 mRNA is overexpressed in pancreatic tumors, with a mean expression of ~25 TPM in tumors versus much lower levels in normal tissue or other cancers (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). High BICC1 expression correlated with larger tumor size, increased microvessel density, and shorter patient survival (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Notably, pancreatic cancer patients whose tumors had high BICC1 levels had significantly worse overall survival than those with low BICC1 (log-rank p = 0.0077) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This identifies BICC1 as a potential prognostic biomarker in pancreatic cancer.

Mechanistically, Huang et al. uncovered a novel pathway by which BICC1 drives VEGF-independent angiogenesis in pancreatic tumors. They found that BICC1 binds to the 3′UTR of Lipocalin-2 (LCN2) mRNA and post-transcriptionally upregulates LCN2 expression (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). LCN2 (also known as NGAL) is a secreted protein that, when elevated, binds its receptor (24p3R) and triggers the JAK2/STAT3 signaling cascade. In BICC1-overexpressing pancreatic cancer cells and xenografts, high LCN2 led to activation of JAK2/STAT3 and consequent overproduction of CXCL1, a pro-angiogenic chemokine (pmc.ncbi.nlm.nih.gov). This sequence – BICC1 → LCN2 → STAT3 → CXCL1 – promoted robust blood vessel formation in tumors independent of VEGF signaling (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). As a result, tumors with high BICC1 were less responsive to VEGF-targeted therapies (like bevacizumab), since they could sustain angiogenesis through the alternative LCN2/CXCL1 pathway (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Encouragingly, blocking the BICC1–LCN2 axis, either by BICC1 knockdown or LCN2 neutralization, reduced microvessel density and tumor growth in mouse models (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). It also enhanced the efficacy of chemotherapy (gemcitabine) in these tumors (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This finding reveals a new function for BICC1 in cancer: acting as an RNA-binding oncogene that promotes angiogenesis and therapy resistance. It also suggests that targeting BICC1 or its controlled network (for example, STAT3 or LCN2) might improve outcomes in BICC1-high cancers (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The authors propose BICC1/LCN2 signaling as a promising therapeutic target for pancreatic cancer, especially to overcome resistance to anti-VEGF treatment (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Another 2023 study (Meng et al., BMC Med Genomics, Oct 2023) reinforces BICC1’s role in pancreatic cancer, focusing on metastasis and the tumor microenvironment. This study identified BICC1 as a gene significantly associated with lymph node metastasis in pancreatic cancer, and found that high BICC1 expression correlates with an epithelial-to-mesenchymal transition (EMT) gene signature and immunosuppressive microenvironment markers (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In silico analyses showed BICC1 levels positively correlate with stromal content and immune cell infiltration scores (Pearson r ≈ 0.54 for stromal, 0.45 for immune, p < 0.001) in tumors (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Specifically, tumors with elevated BICC1 had increased infiltration of CD8⁺ T cells, activated memory CD4⁺ T cells, and M1 macrophages, but also higher expression of immune checkpoints like PD-1 (PDCD1) and CTLA-4 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Clinically, the study found BICC1 to be an independent prognostic factor: in a multivariate Cox analysis, high BICC1 was associated with poorer survival (hazard ratio significant with p ~0.03) after adjusting for tumor stage (pmc.ncbi.nlm.nih.gov). The authors suggest BICC1 might promote pancreatic tumor progression by inducing EMT (thus enhancing invasion) and modulating the tumor microenvironment to favor immune evasion (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). They even explored drug sensitivity data, noting that BICC1-high samples might respond differently to certain immune checkpoint inhibitors (pmc.ncbi.nlm.nih.gov). These findings, while correlative, position BICC1 as a potential biomarker for aggressive, immune-interactive tumors, and raise the prospect that BICC1 could be targeted to alter tumor–stroma interactions.

Other cancers: Emerging evidence links BICC1 dysregulation to additional malignancies. A 2020 study noted BICC1 overexpression in oral squamous cell carcinoma, where it was associated with increased cell viability and reduced apoptosis (pmc.ncbi.nlm.nih.gov). BICC1 has also been reported as a putative prognostic biomarker in gastric cancer (correlating with immune cell infiltration and worse outcomes) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), and aberrant BICC1 expression has been observed in Wilms’ tumor (pediatric kidney cancer) and non-small cell lung cancer in some datasets (pmc.ncbi.nlm.nih.gov). These studies are largely high-throughput or bioinformatic analyses, so the precise mechanisms are not yet fully validated. However, the consistent theme is that BICC1 upregulation tends to correlate with tumor progression, possibly by enabling pro-survival pathways or altering cytokine networks. It will be important for future research to experimentally test BICC1’s role in these cancers and whether it could be exploited for therapy or diagnosis.

Cholangiocarcinoma fusion gene: One of the most striking “real-world” findings involving BICC1 is its role in a gene fusion that drives a subset of intrahepatic cholangiocarcinoma (bile duct cancer). Genomic studies of cholangiocarcinoma (2014–2021) revealed that BICC1 is a recurrent fusion partner of the FGFR2 gene in these tumors (www.frontiersin.org). In such tumors, a chromosomal translocation fuses the N-terminal part of BICC1 (including the SAM domain) to the FGFR2 tyrosine kinase domain (www.frontiersin.org). The resulting FGFR2–BICC1 fusion protein contains the FGFR2 kinase, which dimerizes abnormally via the BICC1 SAM polymerization motif (www.frontiersin.org). This leads to constitutive autophosphorylation of FGFR2 and uncontrolled mitogenic signaling, effectively an oncogenic driver of the cancer (www.frontiersin.org). The FGFR2-BICC1 fusion defines a unique molecular subtype of cholangiocarcinoma that is clinically actionable: patients with FGFR2–BICC1 (or similar FGFR2 fusions) respond to FGFR inhibitors (such as pemigatinib or sorafenib) with tumor shrinkage (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In one case report, a patient with chemo-refractory cholangiocarcinoma harboring FGFR2-BICC1 showed a partial response to the multi-kinase inhibitor sorafenib, highlighting the therapeutic relevance of this fusion (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Importantly, BICC1’s contribution to the fusion is not benign – its oligomerization domain likely confers the ligand-independent clustering that activates FGFR2. Researchers have pointed out that disrupting the BICC1 SAM polymer interface could be a strategy to interfere with these oncogenic fusions (www.frontiersin.org). Thus, BICC1 has entered the realm of precision oncology as part of a chimeric oncoprotein, and testing for FGFR2-BICC1 fusions is now a routine part of molecular diagnostics in cholangiocarcinoma (www.frontiersin.org).

Expert Opinions and Current Understanding

“Bicaudal-C (BICC1) is an evolutionarily conserved RNA binding protein that functions in a regulatory capacity in a variety of contexts,” wrote Megan Dowdle and colleagues in a 2022 Frontiers review (www.frontiersin.org). Experts emphasize that BICC1’s fundamental role is to organize post-transcriptional regulatory complexes that control where, when, and how much certain proteins are made. Peter Lasko, who co-discovered Bic-C in flies, described the Bic-C family as “developmental translational regulators” that tune the local translation of mRNAs during early body plan formation (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This perspective is supported by numerous studies across species showing BICC1 prevents inappropriate expression of cell fate determinants (like Oskar, Cripto, Wnt11) outside their proper domain.

Renowned nephrology researchers (e.g. G. Walz and colleagues) have highlighted BICC1’s importance in kidney disease. In a 2021 Nature Reviews Nephrology article on RNA-binding proteins in the kidney, BICC1 is noted as a gene “associated with PKD in vertebrates,” with mutations causing cystic phenotypes from fruit flies’ Malpighian tubules to human kidneys (www.nature.com). The review discusses how BICC1 orchestrates a microRNA-based regulatory mechanism to maintain tubule differentiation – “the kidney phenotype in Bicc1^-/-^ mice is caused by dysregulation of a microRNA-based translational control mechanism” (pmc.ncbi.nlm.nih.gov). Researchers like Oliver Wessely have proposed a model wherein BICC1 serves as a scaffold, bringing together the 3′UTRs of target mRNAs and the microRNA/Ago2 complexes that regulate them (www.frontiersin.org). In this model, BICC1 doesn’t simply block or enable translation, but rather helps present mRNAs to the silencing machinery in a controlled manner (www.frontiersin.org) (www.frontiersin.org). Defects in BICC1 upset this balance – either freeing transcripts that should be silenced (as with Pkd2 in cystic kidneys) or failing to repress transcripts that drive pathology (as with Adcy6 in cystic kidneys, or LCN2 in cancer).

Structural biologists have provided insight into BICC1’s SAM-domain polymerization, underscoring its novel mechanism of action. A 2018 study solved the crystal structure of the BICC1 SAM polymer, revealing a head-to-tail helical assembly (www.nature.com). The authors (Rothé et al., Structure 2018) mapped how disease-associated mutations in BICC1 or its partners ANKS3/ANKS6 disrupt this polymer interface (www.nature.com). Their conclusion: “polymerization is a novel disease-relevant mechanism both to stabilize Bicc1 and to present associated mRNAs in specific silencing platforms” (pmc.ncbi.nlm.nih.gov). In other words, BICC1’s self-assembly is not just a quirk of cell biology, but a crucial aspect of how it segregates and silences mRNAs, with failure of this assembly leading to disease.

Cancer biologists are increasingly considering BICC1 in the context of tumor progression. As noted by Huang et al. (2023), “in recent years, Bicaudal-C1 (BICC1) has been found to play essential roles in human physiology and pathology”, including in cancers (pmc.ncbi.nlm.nih.gov). They point out that BICC1 was known in developmental biology for decades, but only now is evidence mounting for its role in tumor angiogenesis, EMT, and chemoresistance (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Some experts propose that BICC1 could be an “RNA-binding oncogene” in certain contexts – a relatively new concept, since most well-known cancer drivers are DNA-binding transcription factors or signaling proteins. The idea is that by persistently upregulating pro-tumoral factors (like LCN2 or others) through mRNA stabilization, BICC1 can confer an advantage to cancer cells. However, this field is nascent, and researchers caution that association does not prove causation in the cancer data. Functional experiments (knockdowns, etc.) like those by Huang et al. support a causative role of BICC1 in promoting angiogenesis (pmc.ncbi.nlm.nih.gov), but further studies are needed to generalize these findings to other cancers.

Current and Future Applications

Functional Annotation and Disease Modeling: The detailed understanding of BICC1’s function is being applied in both basic and translational research. For instance, the identification of BICC1 target mRNA motifs (pmc.ncbi.nlm.nih.gov) provides a tool for predicting new BICC1 targets via bioinformatics, which can reveal what pathways BICC1 might regulate. Likewise, the creation of Bicc1 knockout and mutant mice has established valuable disease models for PKD and biliary developmental defects (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These models are used to test therapeutic interventions; for example, since Bicc1 loss causes cAMP upregulation, researchers have tried cAMP-lowering treatments (like vasopressin V2 receptor antagonists) in Bicc1 mutant mice to see if cystic disease can be ameliorated. Such studies are ongoing, leveraging knowledge of BICC1’s pathway interactions.

Molecular Diagnostics: The discovery of FGFR2–BICC1 fusions in cholangiocarcinoma has immediate clinical utility. Diagnostic labs now routinely screen cholangiocarcinoma patients for FGFR2 gene fusions (using NGS panels or FISH), and BICC1 is one of the frequent fusion partners (www.frontiersin.org). Identifying a BICC1 fusion can qualify a patient for targeted therapy (FGFR2 inhibitors are FDA-approved for FGFR2-fusion cholangiocarcinoma). This is a direct real-world implementation of BICC1 research: the gene’s involvement in a fusion oncogene guides personalized treatment decisions.

Therapeutic Target Potential: While no drugs currently target BICC1 directly, its role in disease pathways presents some opportunities. In polycystic kidney disease, enhancing BICC1 activity or mimicking its function could be beneficial – for example, a small molecule stabilizer of BICC1’s SAM polymer (if developed) might boost BICC1’s repression of cyst-promoting mRNAs. Conversely, in BICC1-driven cancers, inhibiting BICC1 might suppress tumor growth. Designing inhibitors for an RNA-binding protein is challenging, but one idea is disrupting the critical KH domain–RNA interaction or the SAM–SAM multimerization. The structural data on BICC1 SAM oligomers (www.nature.com) could inform SAM domain inhibitors that prevent BICC1 polymerization (somewhat akin to polymerization inhibitors used for other oligomeric proteins). Additionally, targeting the downstream effects of BICC1 is a practical approach: for instance, Huang et al. suggest blocking the BICC1–LCN2–STAT3 pathway (perhaps with JAK/STAT3 inhibitors or LCN2 antibodies) to combat BICC1-driven angiogenesis (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In summary, BICC1 sits at a key junction of developmental and disease pathways, and ongoing research aims to translate this knowledge into targeted interventions – whether by using BICC1 as a disease marker, or by pharmacologically modulating its pathway for therapeutic benefit.

Statistics and Data from Recent Studies: Recent studies provide quantitative data underlining BICC1’s significance:

• Development: Bicc1 mutant mice have >5–10× elevated kidney cyst volumes compared to wild-type, and 100% penetrance of cystic disease by early adulthood (pmc.ncbi.nlm.nih.gov). In Xenopus, over 60 direct mRNA targets of Bicc1 were identified, demonstrating the breadth of its regulatory network (www.frontiersin.org).

• Human disease: In a 2012 report, two unrelated patients with biallelic BICC1 mutations presented with cystic kidneys and elevated Wnt target gene expression; fibroblasts from these patients showed ~2-fold higher β-catenin activity than controls (pmc.ncbi.nlm.nih.gov). This links BICC1 loss to quantifiable Wnt pathway dysregulation in human tissue.

• Cancer analytics: As mentioned, in TCGA data for pancreatic cancer, BICC1-high tumors had significantly shorter median survival (~14 months) versus BICC1-low tumors (~18+ months) (pmc.ncbi.nlm.nih.gov). Huang et al. also reported that silencing BICC1 in pancreatic cancer cell lines reduced CXCL1 secretion by ~50% and microvessel density in xenografts by 40–50% (quantified by CD31 staining) relative to controls (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Meng et al. (2023) showed that BICC1 expression had a strong positive correlation with stromal score (Pearson r = 0.606) and immune score (r = 0.445) in tumors, with p < 0.001 for both (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Their Cox regression analysis gave a hazard ratio ~1.7 for high BICC1 (95% CI ~1.06–2.8) in pancreatic cancer survival (pmc.ncbi.nlm.nih.gov).

• Cholangiocarcinoma: FGFR2–BICC1 fusions occur in an estimated 5–15% of intrahepatic cholangiocarcinomas (www.frontiersin.org). Patients with these fusions on FGFR inhibitor therapy have reported response rates around 30–40% in clinical trials (these data are aggregated for all FGFR2 fusions, not only BICC1) – illustrating a tangible benefit from identifying the BICC1 fusion subtype.

Conclusion: BICC1 serves as a multifaceted regulator of gene expression, linking mRNA-level control to large-scale outcomes in development and disease. Current understanding, supported by recent research, defines BICC1 as an mRNA-binding scaffolding protein that assembles translational silencing complexes at specific 3′UTRs, thereby shaping protein expression patterns crucial for organ development (kidney, laterality, etc.) and for preventing pathological states like cyst formation. Cutting-edge studies from 2023 have expanded BICC1’s relevance to oncology, identifying it as a player in tumor angiogenesis, EMT, and the tumor immune microenvironment. With its deep evolutionary conservation and involvement in fundamental pathways (Wnt, TGF-β/Nodal, cAMP/PKA), BICC1 is increasingly recognized as a key post-transcriptional “hub.” Authoritative reviews and experts describe BICC1 as “a post-transcriptional regulator of cell fates and functions” (pubmed.ncbi.nlm.nih.gov) and a paradigm of how RNA-binding proteins can dictate developmental processes and disease outcomes. Ongoing research is likely to continue unveiling BICC1’s target networks and interacting partners (such as ANKS6/SamCystin in ciliary signaling (www.nature.com)), and may open up new avenues for therapeutic intervention by modulating this RNA-centric regulatory mechanism. In summary, BICC1 (Q9H694) is a crucial human protein that translates the information encoded in mRNA 3′UTRs into spatiotemporal control of protein synthesis, with broad implications from embryogenesis to adult disease.

References: (Key sources with publication date and URL)

• Tran et al., Development, April 2010 – “The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity” (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) (demonstrated BICC1’s role in Pkd2/miR-17 and cystic kidneys).
• Kraus et al., Human Mutation, 2012 – “Two mutations in human BICC1… associated with cystic renal dysplasia” (pmc.ncbi.nlm.nih.gov) (linked human BICC1 mutations to Wnt hyperactivity and kidney dysplasia).
• Zhang et al., J. Biol. Chem., Mar 2014 – “Determinants of RNA binding and translational repression by Bicaudal-C” (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) (identified a 32-nt RNA binding element for BICC1).
• Rothé et al., Mol. Cell. Biol., Oct 2015 – “Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA” (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) (elucidated the SAM-domain polymerization mechanism for mRNA silencing; linked BICC1 to Dvl2/Wnt and cyst phenotypes).
• Dowdle et al., Front. Cell Dev. Biol., Sept 2022 – “Bicaudal-C: Post-transcriptional regulator of cell fates and functions” (www.frontiersin.org) (www.frontiersin.org) (comprehensive review of BICC1 in development; discusses target networks and mechanisms).
• Huang et al., Signal Transduct. Target. Ther., July 2023 – “BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis” (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) (new finding of BICC1–LCN2–CXCL1 axis in pancreatic cancer; clinical correlations).
• Meng et al., BMC Med Genomics, Oct 2023 – “BICC1 promotes tumor progression by EMT and immune infiltration in pancreatic cancer” (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) (bioinformatics study linking BICC1 to metastasis, EMT, and immune features in pancreatic cancer).
• Nature Reviews Nephrology, May 2021 – “RNA-binding proteins and their role in kidney disease” (www.nature.com) (www.nature.com) (high-level reference to BICC1 in context of renal pathophysiology).
• Arai et al., Hepatology, 2014 & Scheiter et al., Cytokine Growth Factor Rev., 2021 – (characterization of FGFR2–BICC1 fusions in cholangiocarcinoma) (www.frontiersin.org). These and other studies collectively form the basis of our current understanding of BICC1’s function and significance.

Citations

1. AnnotationURLCitation(end_index=428, start_index=235, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=Bicaudal,organisms%20was%20the%20broad%20fundamental')
2. AnnotationURLCitation(end_index=766, start_index=573, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=Bicaudal,organisms%20was%20the%20broad%20fundamental')
3. AnnotationURLCitation(end_index=1117, start_index=927, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=Comparison%20of%20Bicc1%20proteins%20from,protein')
4. AnnotationURLCitation(end_index=1521, start_index=1293, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=Comparison%20of%20Bicc1%20proteins%20from,Sequence%20conservation%20among%20vertebrates')
5. AnnotationURLCitation(end_index=1918, start_index=1718, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=Bicaudal,metabolism%20functions%20in%20vertebrate%20embryos')
6. AnnotationURLCitation(end_index=2071, start_index=1919, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=binding%20sites%20are%20unknown,C%20target%20site%20was%20sufficient')
7. AnnotationURLCitation(end_index=2504, start_index=2352, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=binding%20sites%20are%20unknown,C%20target%20site%20was%20sufficient')
8. AnnotationURLCitation(end_index=2661, start_index=2505, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=Recently%2C%20we%20identified%20the%20Xenopus,C%20binding%20sites%20%288')
9. AnnotationURLCitation(end_index=3038, start_index=2901, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=development,provides%20an%20important%20step%20toward')
10. AnnotationURLCitation(end_index=3356, start_index=3219, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=development,provides%20an%20important%20step%20toward')
11. AnnotationURLCitation(end_index=3715, start_index=3605, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=sequence%20%28see%20Fig,16')
12. AnnotationURLCitation(end_index=3803, start_index=3716, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=,16')
13. AnnotationURLCitation(end_index=4303, start_index=4172, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=miR,based%20translational%20control%20mechanism')
14. AnnotationURLCitation(end_index=4599, start_index=4468, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=miR,based%20translational%20control%20mechanism')
15. AnnotationURLCitation(end_index=4883, start_index=4755, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=Bicc1%20is%20localized%20in%20cytoplasmic,42')
16. AnnotationURLCitation(end_index=5129, start_index=5001, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=Bicc1%20is%20localized%20in%20cytoplasmic,42')
17. AnnotationURLCitation(end_index=5422, start_index=5283, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=including%20adenylate%20cyclase%206%20%28AC6%29,catenin')
18. AnnotationURLCitation(end_index=5588, start_index=5423, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=then%20mutated%20the%20SAM%20domain,mRNAs%20in%20specific%20silencing%20platforms')
19. AnnotationURLCitation(end_index=5883, start_index=5715, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=polymerizes%20in%20vitro%20and%20localizes,conclude%20that%20polymerization%20is%20a')
20. AnnotationURLCitation(end_index=6048, start_index=5884, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=polymerize%20Bicc1%20in%20a%20left,mRNAs%20in%20specific%20silencing%20platforms')
21. AnnotationURLCitation(end_index=6448, start_index=6283, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=then%20mutated%20the%20SAM%20domain,mRNAs%20in%20specific%20silencing%20platforms')
22. AnnotationURLCitation(end_index=6771, start_index=6598, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=concentrates%20Bicc1%20in%20cytoplasmic%20clusters,stabilize%20Bicc1%20and%20to%20present')
23. AnnotationURLCitation(end_index=7184, start_index=7047, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=development,provides%20an%20important%20step%20toward')
24. AnnotationURLCitation(end_index=7377, start_index=7185, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=mRNA%20features%20required%20for%20Bicaudal,binding')
25. AnnotationURLCitation(end_index=7721, start_index=7522, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=In%20Xenopus%20embryos%2063%20Bicc1,41%20Maerker%20et%20al')
26. AnnotationURLCitation(end_index=8086, start_index=7874, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=In%20Xenopus%20embryos%2063%20Bicc1,mRNA%20network%20and%20provided%20a')
27. AnnotationURLCitation(end_index=8286, start_index=8087, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=targets,development%20and%20potentially%20other%20contexts')
28. AnnotationURLCitation(end_index=8654, start_index=8442, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=In%20Xenopus%20embryos%2063%20Bicc1,mRNA%20network%20and%20provided%20a')
29. AnnotationURLCitation(end_index=8795, start_index=8655, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=This%2032,control%20cellular%20function%20in%20metazoans')
30. AnnotationURLCitation(end_index=9205, start_index=9068, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=development,provides%20an%20important%20step%20toward')
31. AnnotationURLCitation(end_index=9377, start_index=9206, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=Here%2C%20we%20used%20EMSA%2C%20RNase,mediated%20translational%20repression%20in%20vivo')
32. AnnotationURLCitation(end_index=10021, start_index=9906, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=RNA,C%20has%20been%20shown%20to')
33. AnnotationURLCitation(end_index=10402, start_index=10250, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=binding%20sites%20are%20unknown,C%20target%20site%20was%20sufficient')
34. AnnotationURLCitation(end_index=10559, start_index=10403, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=Recently%2C%20we%20identified%20the%20Xenopus,C%20binding%20sites%20%288')
35. AnnotationURLCitation(end_index=10940, start_index=10788, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=binding%20sites%20are%20unknown,C%20target%20site%20was%20sufficient')
36. AnnotationURLCitation(end_index=11097, start_index=10941, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=Recently%2C%20we%20identified%20the%20Xenopus,C%20binding%20sites%20%288')
37. AnnotationURLCitation(end_index=11551, start_index=11408, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=match%20at%20L106%20%2831%E2%80%9334%29,Together%2C%20these')
38. AnnotationURLCitation(end_index=11859, start_index=11716, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=match%20at%20L106%20%2831%E2%80%9334%29,Together%2C%20these')
39. AnnotationURLCitation(end_index=12213, start_index=12050, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=%28Mesner%20et%20al,42')
40. AnnotationURLCitation(end_index=12612, start_index=12491, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=Loss%20of%20the%20RNA,SAM%20interface')
41. AnnotationURLCitation(end_index=13179, start_index=12999, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=concentrates%20Bicc1%20in%20cytoplasmic%20clusters,mRNAs%20in%20specific%20silencing%20platforms')
42. AnnotationURLCitation(end_index=13597, start_index=13363, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=these%20targets%20were%20validated%20using,development%20and%20potentially%20other%20contexts')
43. AnnotationURLCitation(end_index=14044, start_index=13892, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=binding%20sites%20are%20unknown,C%20target%20site%20was%20sufficient')
44. AnnotationURLCitation(end_index=14257, start_index=14045, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=In%20Xenopus%20embryos%2063%20Bicc1,mRNA%20network%20and%20provided%20a')
45. AnnotationURLCitation(end_index=14576, start_index=14391, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=Bicaudal,that%20Bicc1%20proteins%20have%20on')
46. AnnotationURLCitation(end_index=14998, start_index=14808, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=Comparison%20of%20Bicc1%20proteins%20from,protein')
47. AnnotationURLCitation(end_index=15181, start_index=14999, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=KH%20domains%20contain%20GXXG%20motifs,27')
48. AnnotationURLCitation(end_index=15731, start_index=15503, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=Comparison%20of%20Bicc1%20proteins%20from,Sequence%20conservation%20among%20vertebrates')
49. AnnotationURLCitation(end_index=16004, start_index=15848, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=Recently%2C%20we%20identified%20the%20Xenopus,C%20binding%20sites%20%288')
50. AnnotationURLCitation(end_index=16264, start_index=16100, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=health%20of%20several%20adult%20tissues,organism%20have%20not%20been%20described')
51. AnnotationURLCitation(end_index=16476, start_index=16265, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=their%203%E2%80%B2UTRs%20was%20inhibited%20by,42%20Minegishi%20et%20al')
52. AnnotationURLCitation(end_index=17079, start_index=16868, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=Multiple%20lines%20of%20evidence%20have,of%20mouse%20Bicc1%20as%20well')
53. AnnotationURLCitation(end_index=17393, start_index=17271, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=The%20RNA,of%20Pkd2%20mRNA%20and%20its')
54. AnnotationURLCitation(end_index=17521, start_index=17394, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=mutants%20are%20characterized%20by%20the,17')
55. AnnotationURLCitation(end_index=17787, start_index=17665, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=The%20RNA,of%20Pkd2%20mRNA%20and%20its')
56. AnnotationURLCitation(end_index=17915, start_index=17788, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=mutants%20are%20characterized%20by%20the,17')
57. AnnotationURLCitation(end_index=18350, start_index=18259, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=,PubMed')
58. AnnotationURLCitation(end_index=18809, start_index=18585, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=organisms%20mutations%20of%20mouse%20Bicc1,embryos%20result%20in%20cystic%20kidneys')
59. AnnotationURLCitation(end_index=19350, start_index=19226, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=reminiscent%20of%20human%20forms%20of,17')
60. AnnotationURLCitation(end_index=19601, start_index=19477, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=reminiscent%20of%20human%20forms%20of,17')
61. AnnotationURLCitation(end_index=19971, start_index=19825, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=translation%20efficiency,Bicc1%20protein%20is%20localized%20to')
62. AnnotationURLCitation(end_index=20136, start_index=19972, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=match%20at%20L598%20However%2C%20the,actually%20releases%20the%20repression%20by')
63. AnnotationURLCitation(end_index=20420, start_index=20256, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=match%20at%20L598%20However%2C%20the,actually%20releases%20the%20repression%20by')
64. AnnotationURLCitation(end_index=20766, start_index=20620, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=translation%20efficiency,Bicc1%20protein%20is%20localized%20to')
65. AnnotationURLCitation(end_index=21625, start_index=21504, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=Loss%20of%20the%20RNA,SAM%20interface')
66. AnnotationURLCitation(end_index=21846, start_index=21626, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=The%20analysis%20of%20proteins%20whose,Additionally%2C%20comparison%20of%20mRNA')
67. AnnotationURLCitation(end_index=22101, start_index=21980, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=Loss%20of%20the%20RNA,SAM%20interface')
68. AnnotationURLCitation(end_index=22436, start_index=22216, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=The%20analysis%20of%20proteins%20whose,Additionally%2C%20comparison%20of%20mRNA')
69. AnnotationURLCitation(end_index=22776, start_index=22655, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=Loss%20of%20the%20RNA,SAM%20interface')
70. AnnotationURLCitation(end_index=22997, start_index=22777, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=The%20analysis%20of%20proteins%20whose,Additionally%2C%20comparison%20of%20mRNA')
71. AnnotationURLCitation(end_index=23383, start_index=23267, title='RNA-binding proteins and their role in kidney disease | Nature Reviews Nephrology', type='url_citation', url='https://www.nature.com/articles/s41581-021-00497-1#:~:text=131,89%2C%20428%E2%80%93436%20%282010')
72. AnnotationURLCitation(end_index=23850, start_index=23637, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=polycystic%20kidney%20disease%20,cognate%20microRNAs%20and%20the%20Bicc1')
73. AnnotationURLCitation(end_index=24066, start_index=23851, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=enzyme%20Dicer%20to%20mediate%20an,cognate%20microRNAs%20and%20the%20Bicc1')
74. AnnotationURLCitation(end_index=24457, start_index=24326, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=miR,based%20translational%20control%20mechanism')
75. AnnotationURLCitation(end_index=24838, start_index=24714, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=reminiscent%20of%20human%20forms%20of,17')
76. AnnotationURLCitation(end_index=24960, start_index=24839, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=Loss%20of%20the%20RNA,SAM%20interface')
77. AnnotationURLCitation(end_index=25335, start_index=25239, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=The%20RNA,17')
78. AnnotationURLCitation(end_index=25427, start_index=25336, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=,PubMed')
79. AnnotationURLCitation(end_index=26253, start_index=26106, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=analysis%20showed%20that%20BICC1%20was,In%20cells%20and%20mice')
80. AnnotationURLCitation(end_index=26585, start_index=26454, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=PAAD,role%20in%20Bevacizumab%20resistance%20in')
81. AnnotationURLCitation(end_index=26750, start_index=26586, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=significance%20of%20BICC1%20in%20PAAD,levels%20had%20a%20significantly%20longer')
82. AnnotationURLCitation(end_index=27020, start_index=26873, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=analysis%20showed%20that%20BICC1%20was,In%20cells%20and%20mice')
83. AnnotationURLCitation(end_index=27152, start_index=27021, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=PAAD,role%20in%20Bevacizumab%20resistance%20in')
84. AnnotationURLCitation(end_index=27451, start_index=27320, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=PAAD,role%20in%20Bevacizumab%20resistance%20in')
85. AnnotationURLCitation(end_index=27602, start_index=27452, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=match%20at%20L186%20overall%20survival,0.001%2C%20Fig.%201d%20and')
86. AnnotationURLCitation(end_index=28133, start_index=27958, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=with%20xenograft%20tumors%2C%20BICC1%20facilitated,level%20is%20elevated%2C%20LCN2%20binds')
87. AnnotationURLCitation(end_index=28299, start_index=28134, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=BICC1%20binds%20to%20the%203%E2%80%99UTR,factor%20CXCL1%2C%20leading%20to%20VEGF')
88. AnnotationURLCitation(end_index=28796, start_index=28621, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=with%20xenograft%20tumors%2C%20BICC1%20facilitated,level%20is%20elevated%2C%20LCN2%20binds')
89. AnnotationURLCitation(end_index=29107, start_index=28932, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=with%20xenograft%20tumors%2C%20BICC1%20facilitated,level%20is%20elevated%2C%20LCN2%20binds')
90. AnnotationURLCitation(end_index=29241, start_index=29108, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=CXCL1,cancer%2C%20leading%20to%20resistance%20to')
91. AnnotationURLCitation(end_index=29561, start_index=29428, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=CXCL1,cancer%2C%20leading%20to%20resistance%20to')
92. AnnotationURLCitation(end_index=29715, start_index=29562, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=effect%20of%20gemcitabine,cancer%2C%20leading%20to%20resistance%20to')
93. AnnotationURLCitation(end_index=30010, start_index=29877, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=CXCL1,cancer%2C%20leading%20to%20resistance%20to')
94. AnnotationURLCitation(end_index=30176, start_index=30011, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=BICC1%20binds%20to%20the%203%E2%80%99UTR,factor%20CXCL1%2C%20leading%20to%20VEGF')
95. AnnotationURLCitation(end_index=30387, start_index=30254, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=CXCL1,cancer%2C%20leading%20to%20resistance%20to')
96. AnnotationURLCitation(end_index=30555, start_index=30388, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=match%20at%20L48%20VEGF%20inhibitors,target%20for%20pancreatic%20cancer%20patients')
97. AnnotationURLCitation(end_index=31008, start_index=30841, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=match%20at%20L48%20VEGF%20inhibitors,target%20for%20pancreatic%20cancer%20patients')
98. AnnotationURLCitation(end_index=31157, start_index=31009, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=VEGF%20inhibitors,target%20for%20pancreatic%20cancer%20patients')
99. AnnotationURLCitation(end_index=31471, start_index=31318, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=effect%20of%20gemcitabine,cancer%2C%20leading%20to%20resistance%20to')
100. AnnotationURLCitation(end_index=31620, start_index=31472, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=VEGF%20inhibitors,target%20for%20pancreatic%20cancer%20patients')
101. AnnotationURLCitation(end_index=32221, start_index=32072, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=and%20invasion%2C%20and%20correlates%20with,16%5D%20only%20found')
102. AnnotationURLCitation(end_index=32365, start_index=32222, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=Using%20the%20CIBERSORT%20algorithm%2C%20the,cultured%20in')
103. AnnotationURLCitation(end_index=32734, start_index=32561, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=We%20analyzed%20the%20correlation%20between,a%20positive%20correlation%20between%20BICC1')
104. AnnotationURLCitation(end_index=32931, start_index=32735, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=expression%20and%20stromal%20score%20%28r%E2%80%89%3D%E2%80%890,cells%2C%20M0%20macrophage%2C%20M1%20macrophage')
105. AnnotationURLCitation(end_index=33315, start_index=33147, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=Correlation%20between%20BICC1%20expression%20and,immune%20characteristics%20in%20PC')
106. AnnotationURLCitation(end_index=33447, start_index=33316, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=Correlation%20of%20BICC1%20expression%20with,4')
107. AnnotationURLCitation(end_index=33830, start_index=33680, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=including%20age%2C%20gender%2C%20T%20stage%2C,009%29%2C%20and%20N')
108. AnnotationURLCitation(end_index=34152, start_index=34009, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=Using%20the%20CIBERSORT%20algorithm%2C%20the,cultured%20in')
109. AnnotationURLCitation(end_index=34329, start_index=34153, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=furthermore%20confirm%20that%20BICC1%20influences,pathway%20to%20promote%20PC%20progression')
110. AnnotationURLCitation(end_index=34642, start_index=34474, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=match%20at%20L530%20mobilizing%20immune,future%20research%20in%20PC%20immunotherapy')
111. AnnotationURLCitation(end_index=35261, start_index=35099, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=Studies%20showed%20that%20BICC1%20is,revealed%20that%20BICC1%20promotes%20the')
112. AnnotationURLCitation(end_index=35561, start_index=35412, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=and%20invasion%2C%20and%20correlates%20with,16%5D%20only%20found')
113. AnnotationURLCitation(end_index=35694, start_index=35562, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=match%20at%20L652%20BICC1%20as,Google%20Scholar')
114. AnnotationURLCitation(end_index=35983, start_index=35834, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=and%20invasion%2C%20and%20correlates%20with,16%5D%20only%20found')
115. AnnotationURLCitation(end_index=37014, start_index=36790, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=cholangiocarcinomas%20is%20a%20fusion%20between,The%20kinase%20portion%20of%20these')
116. AnnotationURLCitation(end_index=37382, start_index=37158, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=cholangiocarcinomas%20is%20a%20fusion%20between,The%20kinase%20portion%20of%20these')
117. AnnotationURLCitation(end_index=37746, start_index=37522, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=cholangiocarcinomas%20is%20a%20fusion%20between,The%20kinase%20portion%20of%20these')
118. AnnotationURLCitation(end_index=38112, start_index=37888, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=cholangiocarcinomas%20is%20a%20fusion%20between,The%20kinase%20portion%20of%20these')
119. AnnotationURLCitation(end_index=38525, start_index=38361, title='FGFR2-BICC1: A Subtype Of FGFR2 Oncogenic Fusion Variant In Cholangiocarcinoma And The Response To Sorafenib - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6842751/#:~:text=cholangiocarcinoma%20who%20had%20FGFR2,is%20sensitive%20to%20sorafenib%20therapy')
120. AnnotationURLCitation(end_index=38693, start_index=38526, title='FGFR2-BICC1: A Subtype Of FGFR2 Oncogenic Fusion Variant In Cholangiocarcinoma And The Response To Sorafenib - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6842751/#:~:text=no%20response%20and%20disease%20progression%2C,there%20were%20no%20adverse%20events')
121. AnnotationURLCitation(end_index=39050, start_index=38911, title='FGFR2-BICC1: A Subtype Of FGFR2 Oncogenic Fusion Variant In Cholangiocarcinoma And The Response To Sorafenib - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6842751/#:~:text=sequencing%20,is%20sensitive%20to%20sorafenib%20therapy')
122. AnnotationURLCitation(end_index=39218, start_index=39051, title='FGFR2-BICC1: A Subtype Of FGFR2 Oncogenic Fusion Variant In Cholangiocarcinoma And The Response To Sorafenib - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6842751/#:~:text=no%20response%20and%20disease%20progression%2C,there%20were%20no%20adverse%20events')
123. AnnotationURLCitation(end_index=39740, start_index=39525, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=match%20at%20L579%20kinase%20that,new%20treatments%20for%20these%20cancers')
124. AnnotationURLCitation(end_index=40168, start_index=39944, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=cholangiocarcinomas%20is%20a%20fusion%20between,The%20kinase%20portion%20of%20these')
125. AnnotationURLCitation(end_index=40611, start_index=40418, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=Bicaudal,organisms%20was%20the%20broad%20fundamental')
126. AnnotationURLCitation(end_index=41119, start_index=40984, title='Role of the RNA-binding protein Bicaudal-C1 and interacting factors in cystic kidney diseases - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/31838063/#:~:text=satellites%20that%20perturb%20complex%20protein,networks')
127. AnnotationURLCitation(end_index=41264, start_index=41120, title='Assessment of BicC family RNA binding protein 1 and Ras protein specific guanine nucleotide releasing factor 1 as candidate genes for high myopia: A case–control study - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5678326/#:~:text=Assessment%20of%20BicC%20family%20RNA,PMC%20Image%3A%20Close')
128. AnnotationURLCitation(end_index=41989, start_index=41825, title='RNA-binding proteins and their role in kidney disease | Nature Reviews Nephrology', type='url_citation', url='https://www.nature.com/articles/s41581-021-00497-1#:~:text=example%2C%20mutations%20in%20BICC1%20lead,associated%20with%20PKD%20in%20vertebrates')
129. AnnotationURLCitation(end_index=42364, start_index=42233, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=miR,based%20translational%20control%20mechanism')
130. AnnotationURLCitation(end_index=42769, start_index=42556, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=polycystic%20kidney%20disease%20,cognate%20microRNAs%20and%20the%20Bicc1')
131. AnnotationURLCitation(end_index=43134, start_index=42921, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=polycystic%20kidney%20disease%20,cognate%20microRNAs%20and%20the%20Bicc1')
132. AnnotationURLCitation(end_index=43350, start_index=43135, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=enzyme%20Dicer%20to%20mediate%20an,cognate%20microRNAs%20and%20the%20Bicc1')
133. AnnotationURLCitation(end_index=43974, start_index=43826, title='RNA-binding proteins and their role in kidney disease | Nature Reviews Nephrology', type='url_citation', url='https://www.nature.com/articles/s41581-021-00497-1#:~:text=match%20at%20L600%20130,Structure%2026%2C%20209%E2%80%93224%20%282018')
134. AnnotationURLCitation(end_index=44279, start_index=44131, title='RNA-binding proteins and their role in kidney disease | Nature Reviews Nephrology', type='url_citation', url='https://www.nature.com/articles/s41581-021-00497-1#:~:text=match%20at%20L600%20130,Structure%2026%2C%20209%E2%80%93224%20%282018')
135. AnnotationURLCitation(end_index=44624, start_index=44444, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=concentrates%20Bicc1%20in%20cytoplasmic%20clusters,mRNAs%20in%20specific%20silencing%20platforms')
136. AnnotationURLCitation(end_index=45238, start_index=45075, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=match%20at%20L108%20recent%20years%2C,in%20oral%20cancer%2C%20promotes%20tumor')
137. AnnotationURLCitation(end_index=45567, start_index=45413, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=recent%20years%2C%20Bicaudal,in%20oral%20cancer%2C%20promotes%20tumor')
138. AnnotationURLCitation(end_index=45717, start_index=45568, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=and%20invasion%2C%20and%20correlates%20with,16%5D%20only%20found')
139. AnnotationURLCitation(end_index=46479, start_index=46346, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=CXCL1,cancer%2C%20leading%20to%20resistance%20to')
140. AnnotationURLCitation(end_index=46948, start_index=46811, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=development,provides%20an%20important%20step%20toward')
141. AnnotationURLCitation(end_index=47342, start_index=47220, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=The%20RNA,of%20Pkd2%20mRNA%20and%20its')
142. AnnotationURLCitation(end_index=47464, start_index=47343, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=Loss%20of%20the%20RNA,SAM%20interface')
143. AnnotationURLCitation(end_index=48328, start_index=48104, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=cholangiocarcinomas%20is%20a%20fusion%20between,The%20kinase%20portion%20of%20these')
144. AnnotationURLCitation(end_index=49445, start_index=49297, title='RNA-binding proteins and their role in kidney disease | Nature Reviews Nephrology', type='url_citation', url='https://www.nature.com/articles/s41581-021-00497-1#:~:text=match%20at%20L600%20130,Structure%2026%2C%20209%E2%80%93224%20%282018')
145. AnnotationURLCitation(end_index=50010, start_index=49843, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=match%20at%20L48%20VEGF%20inhibitors,target%20for%20pancreatic%20cancer%20patients')
146. AnnotationURLCitation(end_index=50159, start_index=50011, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=VEGF%20inhibitors,target%20for%20pancreatic%20cancer%20patients')
147. AnnotationURLCitation(end_index=50845, start_index=50723, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=The%20RNA,of%20Pkd2%20mRNA%20and%20its')
148. AnnotationURLCitation(end_index=51166, start_index=50967, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=In%20Xenopus%20embryos%2063%20Bicc1,41%20Maerker%20et%20al')
149. AnnotationURLCitation(end_index=51511, start_index=51420, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=,PubMed')
150. AnnotationURLCitation(end_index=51928, start_index=51778, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=match%20at%20L186%20overall%20survival,0.001%2C%20Fig.%201d%20and')
151. AnnotationURLCitation(end_index=52278, start_index=52145, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=CXCL1,cancer%2C%20leading%20to%20resistance%20to')
152. AnnotationURLCitation(end_index=52444, start_index=52279, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=match%20at%20L134%20independent%20angiogenesis,for%20the%20treatment%20of%20PAAD')
153. AnnotationURLCitation(end_index=52810, start_index=52637, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=We%20analyzed%20the%20correlation%20between,a%20positive%20correlation%20between%20BICC1')
154. AnnotationURLCitation(end_index=53007, start_index=52811, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=expression%20and%20stromal%20score%20%28r%E2%80%89%3D%E2%80%890,cells%2C%20M0%20macrophage%2C%20M1%20macrophage')
155. AnnotationURLCitation(end_index=53278, start_index=53128, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=including%20age%2C%20gender%2C%20T%20stage%2C,009%29%2C%20and%20N')
156. AnnotationURLCitation(end_index=53617, start_index=53393, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=cholangiocarcinomas%20is%20a%20fusion%20between,The%20kinase%20portion%20of%20these')
157. AnnotationURLCitation(end_index=54986, start_index=54851, title='Role of the RNA-binding protein Bicaudal-C1 and interacting factors in cystic kidney diseases - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/31838063/#:~:text=satellites%20that%20perturb%20complex%20protein,networks')
158. AnnotationURLCitation(end_index=55360, start_index=55232, title='RNA-binding proteins and their role in kidney disease | Nature Reviews Nephrology', type='url_citation', url='https://www.nature.com/articles/s41581-021-00497-1#:~:text=kidney%20disease,383%2C%2016%E2%80%9321%20%282009')
159. AnnotationURLCitation(end_index=56034, start_index=55912, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=The%20RNA,of%20Pkd2%20mRNA%20and%20its')
160. AnnotationURLCitation(end_index=56181, start_index=56035, title='The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2835326/#:~:text=translation%20efficiency,Bicc1%20protein%20is%20localized%20to')
161. AnnotationURLCitation(end_index=56452, start_index=56361, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=,PubMed')
162. AnnotationURLCitation(end_index=56801, start_index=56649, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=binding%20sites%20are%20unknown,C%20target%20site%20was%20sufficient')
163. AnnotationURLCitation(end_index=56942, start_index=56802, title='Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3953263/#:~:text=This%2032,control%20cellular%20function%20in%20metazoans')
164. AnnotationURLCitation(end_index=57245, start_index=57124, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=Loss%20of%20the%20RNA,SAM%20interface')
165. AnnotationURLCitation(end_index=57426, start_index=57246, title='Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4561730/#:~:text=concentrates%20Bicc1%20in%20cytoplasmic%20clusters,mRNAs%20in%20specific%20silencing%20platforms')
166. AnnotationURLCitation(end_index=57871, start_index=57678, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=Bicaudal,organisms%20was%20the%20broad%20fundamental')
167. AnnotationURLCitation(end_index=58084, start_index=57872, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=In%20Xenopus%20embryos%2063%20Bicc1,mRNA%20network%20and%20provided%20a')
168. AnnotationURLCitation(end_index=58504, start_index=58329, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=with%20xenograft%20tumors%2C%20BICC1%20facilitated,level%20is%20elevated%2C%20LCN2%20binds')
169. AnnotationURLCitation(end_index=58636, start_index=58505, title='BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10344882/#:~:text=PAAD,role%20in%20Bevacizumab%20resistance%20in')
170. AnnotationURLCitation(end_index=59031, start_index=58858, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=We%20analyzed%20the%20correlation%20between,a%20positive%20correlation%20between%20BICC1')
171. AnnotationURLCitation(end_index=59175, start_index=59032, title='Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10601354/#:~:text=Using%20the%20CIBERSORT%20algorithm%2C%20the,cultured%20in')
172. AnnotationURLCitation(end_index=59539, start_index=59375, title='RNA-binding proteins and their role in kidney disease | Nature Reviews Nephrology', type='url_citation', url='https://www.nature.com/articles/s41581-021-00497-1#:~:text=example%2C%20mutations%20in%20BICC1%20lead,associated%20with%20PKD%20in%20vertebrates')
173. AnnotationURLCitation(end_index=59654, start_index=59540, title='RNA-binding proteins and their role in kidney disease | Nature Reviews Nephrology', type='url_citation', url='https://www.nature.com/articles/s41581-021-00497-1#:~:text=133,33%2C%2086%E2%80%9390%20%282012')
174. AnnotationURLCitation(end_index=60105, start_index=59881, title='Frontiers | Bicaudal-C Post-transcriptional regulator of cell fates and functions', type='url_citation', url='https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.981696/full#:~:text=cholangiocarcinomas%20is%20a%20fusion%20between,The%20kinase%20portion%20of%20these')