Affinage

HNRNPC

Heterogeneous nuclear ribonucleoproteins C1/C2 · UniProt P07910

Length
306 aa
Mass
33.7 kDa
Annotated
2026-04-28
89 papers in source corpus 31 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HNRNPC is an abundant nuclear RNA-binding protein that self-assembles into tetramers via its C-terminal domain and recognizes poly-U-rich sequences and m6A-modified motifs in pre-mRNAs and lncRNAs to regulate alternative splicing, alternative polyadenylation, mRNA stability, and miRNA processing across diverse cellular contexts (PMID:23192344, PMID:31147722, PMID:34271104, PMID:35729324). By binding Alu-containing intronic sequences, HNRNPC suppresses the accumulation of endogenous dsRNA that would otherwise activate RIG-I/MDA5-dependent innate immune signaling, and it modulates STING stability through K48-linked ubiquitination to further dampen type I interferon responses (PMID:30158112, PMID:34297039, PMID:39994817). HNRNPC directly binds and destabilizes p53 protein under basal conditions—a function competed by lncRNAs such as SNHG1 and DANCR—and its own stability and RNA-binding activity are tuned by post-translational modifications including tyrosine phosphorylation (regulated by DUSP3), K48-ubiquitination (by CUL9 or FBXW11), lysine crotonylation at K189, and lysine lactylation at K176 (PMID:28264987, PMID:38538536, PMID:35505093, PMID:40482911, PMID:41435694). HNRNPC haploinsufficiency causes intellectual-disability-associated alternative splicing defects and impaired neuronal arborization, and germ-cell-specific knockout arrests meiosis at the pachytene stage, establishing dose-sensitive developmental roles (PMID:37541189, PMID:39921484).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2012 High

    Establishing that HNRNPC forms tetramers through a discrete C-terminal self-assembly domain, independent of RNA binding, provided the structural basis for its cooperative polymerization on target transcripts.

    Evidence In vitro reconstitution with deletion mapping and size-exclusion chromatography in human/yeast systems

    PMID:23192344

    Open questions at the time
    • No high-resolution structure of the tetramerization domain
    • Functional consequence of disrupting tetramerization on splicing not tested in cells
  2. 2017 High

    Demonstrating that HNRNPC directly binds and destabilizes p53 protein, and that lncRNA SNHG1 competes for HNRNPC binding to release p53 upon DNA damage, established a non-RNA-processing function: regulation of p53 protein turnover.

    Evidence Reciprocal Co-IP, RNA pulldown, siRNA knockdown, and p53 stability/apoptosis assays in cancer cells

    PMID:28264987

    Open questions at the time
    • Whether HNRNPC directly ubiquitinates p53 or recruits an E3 ligase was unresolved
    • Generality beyond the specific cancer cell lines used not tested
  3. 2018 High

    Revealing that HNRNPC binds Alu-containing intronic dsRNA and its depletion triggers accumulation of endogenous dsRNA activating RIG-I-mediated interferon responses answered how cells prevent self-RNA-driven innate immune activation.

    Evidence siRNA knockdown, RNA-seq, RIP, dsRNA immunofluorescence, and RIG-I reporter assays in breast cancer cells

    PMID:30158112

    Open questions at the time
    • Whether MDA5 was also involved was not addressed (later resolved)
    • Mechanism by which HNRNPC prevents dsRNA formation versus masking dsRNA from sensors unclear
  4. 2019 High

    Identifying HNRNPC as a regulator of alternative cleavage and polyadenylation (APA) expanded its RNA-processing repertoire beyond splicing to include 3′-end formation, with cancer-specific APA profiles established by HNRNPC overexpression.

    Evidence 3′-seq APA profiling with HNRNPC overexpression/knockdown and subcellular fractionation in colon cancer cells

    PMID:31147722

    Open questions at the time
    • Whether HNRNPC binds APA sites directly or acts indirectly through other cleavage/polyadenylation factors not resolved
    • Overlap with m6A-dependent regulation at APA sites unexplored
  5. 2021 High

    Convergent studies established HNRNPC as an m6A-dependent alternative splicing regulator (m6A reader) and extended the dsRNA-suppression model to MDA5 and ADAR epistasis: m6A site mutagenesis on TAF8 abolished HNRNPC interaction and altered metastatic splicing, while HNRNPC/ADAR double depletion synergistically activated MDA5-dependent interferon responses via Alu-derived dsRNA.

    Evidence m6A site mutagenesis, MeRIP-seq, RIP, in vivo metastasis models (TAF8); CRISPR/siRNA double KD, eCLIP, MDA5 epistasis in THP-1 monocytes; U-tract mutagenesis on Tau pre-mRNA

    PMID:34271104 PMID:34297039 PMID:34965173

    Open questions at the time
    • Whether HNRNPC reads m6A directly or via m6A-induced RNA structural switch ('m6A-switch') was debated
    • Structural basis of m6A recognition not determined
  6. 2022 Medium

    Multiple studies defined post-translational control of HNRNPC: DUSP3-mediated tyrosine dephosphorylation reduces RNA-binding affinity and modulates IRES-dependent translation; CUL9/p53-mediated K48-ubiquitination targets HNRNPC for proteasomal degradation; and HNRNPC stabilizes HIF1A mRNA and influences Drosha-dependent isomiR biogenesis, broadening its functional scope to translational regulation, ferroptosis resistance, and miRNA processing.

    Evidence Phospho-specific western blot and ribosome fractionation (DUSP3); Co-IP and ubiquitination assays (CUL9); mRNA stability assays (HIF1A); small-RNA-seq and KD (isomiR-21)

    PMID:35505093 PMID:35729324 PMID:35848884 PMID:38538536

    Open questions at the time
    • Tyrosine phosphorylation sites on HNRNPC not mapped
    • Whether CUL9 ubiquitinates HNRNPC directly or via a scaffold complex unclear
    • isomiR mechanism at the structural level not resolved
  7. 2022 High

    Discovery that HNRNPC relocates to the sarcomeric Z-disc in pathologically remodeled cardiomyocytes, where it associates with translation machinery and regulates mechanotransduction-related alternative splicing (including YAP1), revealed a tissue-specific, localization-dependent splicing role outside the canonical nuclear context.

    Evidence Immunofluorescence, CLIP-seq, proximity ligation, and cardiac failure models with hnRNPC KD

    PMID:36417487

    Open questions at the time
    • What drives HNRNPC relocalization to the Z-disc not identified
    • Whether Z-disc-localized HNRNPC binds mRNAs co-translationally or post-transcriptionally unclear
  8. 2023 High

    Human genetic evidence established that HNRNPC haploinsufficiency causes a neurodevelopmental syndrome: patient-derived cells showed an alternative splicing signature enriched in intellectual disability genes, and both decreased and increased HNRNPC levels impaired neuronal arborization and migration, indicating dose-sensitivity.

    Evidence iPSC/fibroblast RNA-seq from affected individuals, meta-analysis across three cell lines, neuronal functional assays

    PMID:37541189

    Open questions at the time
    • Specific causal splice target(s) driving the neurodevelopmental phenotype not identified
    • Whether intellectual disability results from splicing, mRNA stability, or combined defects unknown
  9. 2024 Medium

    Multiple m6A-dependent splicing and mRNA stabilization targets were validated (FOXM1 in cervical cancer, IRAK1 in glioma, WDR77 in breast cancer, PKM in thyroid carcinoma, TFAP2A in breast cancer), consolidating HNRNPC's role as a widespread m6A reader with context-specific oncogenic outputs, and non-degradative ubiquitination was shown to regulate HNRNPC nuclear import via a Vimentin/Importin-α7 complex.

    Evidence m6A site mutagenesis, MeRIP, RIP, splicing assays, mRNA stability assays, and subcellular fractionation across multiple cancer types

    PMID:37528369 PMID:38184608 PMID:38353359 PMID:38830885 PMID:39375330 PMID:39380010

    Open questions at the time
    • Whether all m6A-dependent targets use the same m6A-switch mechanism not tested
    • Relative contribution of splicing versus mRNA stability to each target's regulation unresolved
    • The E3 ligase mediating non-degradative ubiquitination for nuclear import not identified
  10. 2025 Medium

    Site-specific post-translational modifications—K189 crotonylation (regulated by MDM2/HDAC3) and K176 lactylation—were shown to directly modulate HNRNPC's RNA-binding affinity and mRNA-stabilizing function, establishing a PTM code that tunes HNRNPC output; germ-cell-specific knockout demonstrated essential roles in meiotic progression at the pachytene stage; and HNRNPC was found to promote STING degradation via K48-ubiquitination to suppress innate immunity during viral infection.

    Evidence Crotonylome/lactylome MS with site-specific mutants (K189Q/R, K176), conditional KO mice with histology and RIP, Co-IP with K48-ubiquitination assays, and FBXW11 E3 ligase identification

    PMID:39921484 PMID:39994817 PMID:40482911 PMID:41037014 PMID:41435694

    Open questions at the time
    • Crosstalk between crotonylation and lactylation at adjacent sites not examined
    • Whether K189Cr and K176la are mutually exclusive or co-occurring is unknown
    • Mechanism by which HNRNPC promotes STING ubiquitination (direct E3 activity vs. scaffold) unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of HNRNPC's m6A recognition (direct binding vs. RNA structural switch), the full PTM code integrating phosphorylation, ubiquitination, crotonylation, and lactylation, and how HNRNPC selects between its splicing, mRNA stability, and translational regulatory functions in different cellular contexts.
  • No high-resolution structure of HNRNPC bound to m6A-containing RNA
  • No systematic mapping of all functional PTM sites
  • Mechanism of context-dependent functional switching (splicing vs. stability vs. translation) unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 9 GO:0140098 catalytic activity, acting on RNA 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-8953854 Metabolism of RNA 7 R-HSA-392499 Metabolism of proteins 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3
Partners
CUL9DUSP3ELAVL1FBXW11HNRNPKPTBP1TP53UPF1
Complex memberships
HNRNPC/Vimentin/Importin-α7 complexhnRNP C tetramer

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 HNRNPC binds intron-derived Alu-containing dsRNA in pre-mRNA introns; its depletion in breast cancer cells causes accumulation of endogenous dsRNA that activates the RIG-I–mediated interferon response, inhibiting cell proliferation and tumor growth. siRNA knockdown with RNA-seq, RNA immunoprecipitation, dsRNA immunofluorescence, RIG-I reporter assays The EMBO journal High 30158112
2019 hnRNPC regulates alternative cleavage and polyadenylation (APA) site selection in a subset of cancer-progression genes (including MTHFD1L) and its overexpression establishes cancer-specific APA profiles in metastatic colon cancer cells. Subcellular fractionation, nuclear/cytoplasmic APA profiling by 3′-seq, hnRNPC overexpression and knockdown Nucleic acids research High 31147722
2017 hnRNPC directly binds p53 protein under basal conditions, destabilizing p53 and preventing its activation. Upon doxorubicin treatment, nuclear-retained lncRNA SNHG1 competes with p53 for hnRNPC binding, releasing p53 to promote apoptosis. Co-IP, RNA immunoprecipitation, RNA pulldown, siRNA knockdown, p53 stability assays, apoptosis assays EMBO reports High 28264987
2021 HNRNPC depletion in hnRNPC-deficient cells (and synergistically with ADAR depletion) causes dysregulation of Alu-containing introns via unmasked cryptic splice sites, generating dsRNA ligands that activate MDA5-dependent type I IFN responses. CRISPR/siRNA knockdown in THP-1 monocytes, RNA-seq, eCLIP, type I IFN reporter assays, MDA5 epistasis experiments The Journal of experimental medicine High 34297039
2021 HNRNPC acts as an m6A reader that impedes anti-metastatic alternative splicing of TAF8 pre-mRNA; it antagonizes the anti-metastatic isoform TAF8L and promotes the pro-metastatic isoform TAF8S. Mutation of the m6A site on TAF8 attenuates the HNRNPC–TAF8 transcript interaction. HNRNPC knockdown/overexpression, MeRIP-seq, splice isoform RT-PCR, m6A site mutagenesis, RIP, in vivo metastasis models Cancer letters High 34271104
2022 hnRNPC is up-regulated upon pathological ECM remodeling in cardiomyocytes and relocates to the sarcomeric Z-disc, an active site of localized translation, where it associates with the translation machinery. Changes in hnRNPC expression, phosphorylation, and localization affect alternative splicing of mechanotransduction mRNAs including YAP1. Immunofluorescence, subcellular fractionation, proximity ligation, CLIP-seq, cardiac failure model, hnRNPC KD Science translational medicine High 36417487
2021 hnRNPC binds poly-uridine (U-tract) sequences in introns 9 and 10 of Tau pre-mRNA to promote Tau exon 10 inclusion; knockdown causes exon 10 skipping and overexpression promotes inclusion. Mutation of U-tract motifs abolishes hnRNPC binding and its effect on splicing. RAP-MS (RNA Antisense Purification with Mass Spectrometry), siRNA/overexpression RT-PCR splicing assay, U-tract mutagenesis, RIP RNA biology High 34965173
2012 The C-terminal self-assembly domain of human hnRNPC enables tetramerization; this region is structurally homologous in yeast Nab3, and the self-assembly mechanism is conserved and independent of RNA binding, allowing cooperative polymerization on target transcripts. Biochemical self-assembly assay, size-exclusion chromatography, deletion mapping, functional yeast genetics The Journal of biological chemistry High 23192344
2022 HNRNPC stabilizes HIF1A mRNA in hepatocellular carcinoma cells; its downregulation decreases HIF1A mRNA stability and reduces HCC invasion/metastasis. IL-6/STAT3 signaling upregulates HNRNPC expression upstream. HNRNPC siRNA/overexpression, mRNA stability assay (actinomycin D), RNA-seq, in vivo metastasis, IL-6 antibody rescue Cancer science Medium 35848884
2022 hnRNPC regulates IRES-dependent translation: DUSP3-mediated tyrosine dephosphorylation of hnRNPC reduces its RNA-binding affinity; when DUSP3 is depleted, tyrosine-hyperphosphorylated hnRNPC preferentially associates with IRES-containing mRNAs within ITAF complexes and enhances IRES-dependent translation of c-MYC and XIAP. Tyrosine-phosphorylated hnRNPC also releases p53 when competing RNAs are present. DUSP3 siRNA KD, phosphorylation-specific western blot, ribosome gradient fractionation, RIP with IRES-containing mRNAs, qPCR for protein vs. mRNA levels Biology of the cell Medium 38538536
2022 CUL9 binds p53 to ubiquitylate HNRNPC and target it for proteasomal degradation; this CUL9-HNRNPC-MATE1 negative-feedback loop provides resistance to erastin-induced ferroptosis in colorectal cancer cells. Co-IP, ubiquitination assay, CUL9 overexpression/KD, ferroptosis assays, HNRNPC protein stability assays Oncogene Medium 35505093
2025 HDAC3 acts as a specific decrotonylase of HNRNPC at K189 (HNRNPCK189Cr); the MDM2/HDAC3 axis controls crotonylation levels. HNRNPCK189Cr stabilizes CCND1 and MCM3 mRNAs to promote colorectal cancer cell proliferation. Activating (K189Q) and inactivating (K189R) mutations confirmed the functional role of this modification. Global crotonylome mass spectrometry, HNRNPCK189Q/K189R mutants, mRNA stability assays, in vivo mouse model, HDAC3 agonist treatment Cancer letters Medium 40482911
2025 Histone H3K18 lactylation drives HNRNPC overexpression in gemcitabine-resistant PDAC. HNRNPC stabilizes TRAF6 transcripts in an m6A-dependent manner, activating autophagy, and also stabilizes ALDH1A3 mRNA, enhancing glycolysis and H3K18la levels—creating a positive feedback loop sustaining chemoresistance. Multi-omics (RNA-seq, ChIP, MeRIP), HNRNPC KD, patient-derived xenograft model, ALDH1A3 inhibitor (673A) treatment Advanced science Medium 41309519
2025 hnRNPC functions with HuR (ELAVL1) to directly bind and modulate m6A-dependent alternative splicing of meiotic-related genes (Sycp1, Brca1, Smc5) during spermatogenesis; germ-cell-specific knockout causes meiotic arrest at pachytene stage in both male and female mice. Conditional Hnrnpc knockout mice, RIP, alternative splicing RT-PCR, histology, Co-IP of hnRNPC–HuR Advanced science High 39921484
2024 HNRNPC promotes FOXM1 exon skipping by binding m6A-modified motifs in FOXM1 pre-mRNA, generating a metastasis-promoting FOXM1-S variant; m6A site mutation on FOXM1 weakens HNRNPC–FOXM1 pre-RNA interaction and reduces FOXM1-S production, inhibiting lymphatic metastasis in cervical cancer. HNRNPC KD/overexpression, MeRIP-qPCR, m6A site mutagenesis, splice isoform RT-PCR, in vitro invasion/migration assays Cell death & disease High 39375330
2023 HNRNPC haploinsufficiency alters alternative splicing of multiple intellectual disability-associated genes; the meta-analysis across three cell lines defines a ubiquitous HNRNPC-dependent alternative splicing signature enriched for ID genes. Decreased or increased HNRNPC levels both impair neuronal arborization and migration. iPSC/fibroblast RNA-seq from affected individuals, meta-analysis of published RNA-seq datasets, neuronal arborization and migration assays American journal of human genetics High 37541189
2022 hnRNPC induces production of a cancer-specific 5′-isomiR (isomiR-21-5p|±1) by binding a poly-U motif upstream of pre-miR-21 and influencing Drosha processing; this isomiR suppresses GHR and promotes hepatocellular carcinoma. High-throughput small-RNA sequencing, hnRNPC KD/overexpression, antagomir treatment, GHR reporter assay, mouse liver cancer model Experimental & molecular medicine Medium 35729324
2024 hnRNPC interacts with influenza A nucleoprotein (NP) via its C-terminal auxiliary domain; hnRNPC negatively regulates influenza viral growth and its interaction with NP promotes host cell apoptosis during infection. Co-IP, domain mapping with deletion mutants, viral growth assays, apoptosis assays across influenza A subtypes International journal of molecular sciences Medium 36362400
2024 circPPAP2B interacts with HNRNPC in an m6A-dependent manner to facilitate HNRNPC nuclear translocation, which is dependent on non-degradative ubiquitination of HNRNPC and stabilization of an HNRNPC/Vimentin/Importin α7 ternary complex. HNRNPC nuclear redistribution modulates its interaction with splicing factors PTBP1 and HNRNPK to regulate alternative splicing in ccRCC. RNA pulldown, mass spectrometry, RIP, Co-IP, MeRIP, immunofluorescence subcellular fractionation, next-generation RNA-seq Molecular cancer Medium 38184608
2022 LNCRNA CEBPA-DT binds hnRNPC and facilitates its cytoplasmic translocation, where hnRNPC interacts with and stabilizes DDR2 mRNA, promoting DDR2 expression and subsequent DDR2/β-catenin signaling and EMT in HCC. RNA FISH, RIP, RNA pulldown, immunofluorescence, subcellular protein fractionation, Co-IP, hnRNPC KD Journal of experimental & clinical cancer research Medium 36471363
2025 hnRNPC promotes SVCV (and influenza) replication by interacting with MITA (STING) via its C-terminal domain and activating K48-linked ubiquitination of MITA for degradation, thus suppressing type I IFN responses. Human hnRNPC similarly decreases MITA protein, indicating conserved function. Co-IP, ubiquitination assay (K48-specific), domain mapping, hnRNPC overexpression in HEK293 cells, viral replication assays in zebrafish and human cells Veterinary research Medium 39994817
2025 hnRNPC acts as a potent TDP-43 splicing regulator; modulation of TDP-43 or hnRNPC levels can rescue cryptic exon splicing associated with TDP-43 loss of function in ALS/FTLD models. Proximity labeling (APEX2), mass spectrometry interactome, snRNA-seq of patient tissue, functional splicing rescue assays bioRxivpreprint Low
2025 During mitosis, hnRNPC redistributes from intron binding to binding 3′-UTRs of mature mRNAs on polysomes; it forms two density-distinct RNP populations (LD and HD) with co-migrating ribosomes, and its depletion globally reduces mitotic mRNA abundance, indicating a role as a mitotic mRNA stabilizer. Cell cycle synchronization, density gradient sedimentation, RNA-seq, fCLIP, hnRNPC KD bioRxivpreprint Low
2024 EGF-induced recruitment of UPF1 adjacent to HNRNPC on mRNAs effects splicing surveillance of cell proliferation mRNAs; simultaneous HNRNPC and UPF1 co-binding on RND3 and DDX3X mRNAs was confirmed by sequential Re-CLIP immunoprecipitation. irCLIP-RNP (CLIP + mass spectrometry for co-bound proteins), Re-CLIP (sequential immunoprecipitation CLIP), EGF stimulation bioRxivpreprint Low
2025 HNRNPC lacytylation at K176 (K176la) strengthens its binding to poly-U motifs in PAK6 pre-mRNA, facilitating expression of the oncogenic PAK6S isoform and promoting pancreatic cancer growth and metastasis; blocking K176la inhibits these phenotypes. Crotonylome/lactylome MS, K176 site-specific mutants, RNA binding assays, in vivo tumor models Cancer letters Medium 41435694
2023 lncRNA DANCR binds both hnRNPC and p53; DANCR knockdown attenuates hnRNPC–p53 binding, thereby stabilizing p53 and promoting granulosa cell senescence. In vivo Dancr knockout mice show POI phenotypes and fertility decline. RNA pulldown, RIP, Co-IP, Dancr KO mice, cell senescence assays, p53 protein stability assays Journal of ovarian research Medium 36805799
2024 HNRNPC recognizes m6A-modified TFAP2A mRNA (placed by VIRMA) and promotes TFAP2A expression and DDR1 transcription, enhancing collagen fiber alignment and reducing anti-tumor immune cell infiltration in breast cancer. PAR-CLIP, Me-RIP, RIP, ChIP (TFAP2A on DDR1 promoter), dual-luciferase, in vivo mouse transplant model Molecular medicine Medium 37528369
2024 HNRNPC stabilizes WDR77 mRNA in an m6A-dependent manner in breast cancer cells, promoting G1/S cell cycle transition and cell proliferation; the interaction was validated by RIP and actinomycin D mRNA stability assays. RIP, actinomycin D mRNA stability assay, HNRNPC KD/overexpression, m6A modification analysis, xenograft models Molecular carcinogenesis Medium 38353359
2024 HNRNPC modulates PKM pre-mRNA alternative splicing via m6A modification, promoting inclusion of PKM2-generating exons and aerobic glycolysis in papillary thyroid carcinoma cells. HNRNPC KD, RIP-seq, meRIP-qPCR, RT-PCR splicing assay, Seahorse metabolic assay Journal of translational medicine Medium 39380010
2025 FBXW11 acts as the E3 ubiquitin ligase for HNRNPC, ubiquitinating and degrading it in placental cells; in preeclampsia, HNRNPC promotes ACSL3 exon 10 skipping in an m6A-dependent manner (m6A site mutation reduces binding and exon skipping), affecting ferroptosis marker expression. Co-IP, in vitro ubiquitination assay, m6A site mutation, RT-PCR splicing assay, HNRNPC KD in mice Journal of hypertension Medium 41037014
2024 HNRNPC stabilizes IRAK1 mRNA in an m6A-dependent manner in glioma cells, activating the MAPK signaling pathway; integrative RNA-seq and MeRIP-seq identified IRAK1 as a direct downstream target of HNRNPC. HNRNPC KD/overexpression, RNA-seq, MeRIP-seq, RIP, mRNA stability assay, MAPK pathway inhibition, TMAs Cell death & disease Medium 38830885
2025 HNRNPC regulates CELF2 expression through m6A modification; in drug-resistant AML cells, increased HNRNPC decreases CELF2, upregulating glycolysis and mitochondrial dysfunction. Epistasis experiments show CELF2 overexpression reverses HNRNPC-driven glycolysis. HNRNPC/CELF2 siRNA KD/overexpression, glycolysis (ECAR/OCR) assays, m6A modification analysis, invasion assays Cell & bioscience Low 40380235
2024 Sertoli cell-specific conditional knockout of hnRNPC in mice causes aberrant Sertoli cell proliferation, disrupted cytoskeleton, impaired blood-testis barrier function, and defective spermiogenesis, demonstrating a cell-autonomous role for hnRNPC in supporting germ cell development. Conditional Hnrnpc KO (Sertoli cell-specific), histology, RNA-seq, blood-testis barrier functional assays Biology of reproduction Medium 38590182
2025 HNF4A-AS1 mediates an interaction between hnRNPC and HNF4A protein, and hnRNPC promotes HNF4A degradation through ubiquitination, thereby decreasing CYP3A4 expression and alleviating ritonavir-induced liver injury. RNA pulldown, RIP, Co-IP, in vitro ubiquitination assay, liver-specific Hnf4aos KO mice, western blot, ALT/AST measurement Molecular pharmacology Medium 40037142

Source papers

Stage 0 corpus · 89 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Function of HNRNPC in breast cancer cells by controlling the dsRNA-induced interferon response. The EMBO journal 161 30158112
2019 hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles. Nucleic acids research 99 31147722
2017 Nuclear retention of the lncRNA SNHG1 by doxorubicin attenuates hnRNPC-p53 protein interactions. EMBO reports 89 28264987
2018 MiR-744-5p inducing cell death by directly targeting HNRNPC and NFIX in ovarian cancer cells. Scientific reports 85 29899543
2022 lncRNA CYTOR promotes aberrant glycolysis and mitochondrial respiration via HNRNPC-mediated ZEB1 stabilization in oral squamous cell carcinoma. Cell death & disease 72 35963855
2021 HNRNPC impedes m6A-dependent anti-metastatic alternative splicing events in pancreatic ductal adenocarcinoma. Cancer letters 72 34271104
2019 LBX2-AS1 is activated by ZEB1 and promotes the development of esophageal squamous cell carcinoma by interacting with HNRNPC to enhance the stability of ZEB1 and ZEB2 mRNAs. Biochemical and biophysical research communications 60 30824187
2015 HNRNPC as a candidate biomarker for chemoresistance in gastric cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 57 26453116
2017 Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress. Cell death & disease 56 28102850
2024 CircPPAP2B controls metastasis of clear cell renal cell carcinoma via HNRNPC-dependent alternative splicing and targeting the miR-182-5p/CYP1B1 axis. Molecular cancer 53 38184608
2022 HNRNPC downregulation inhibits IL-6/STAT3-mediated HCC metastasis by decreasing HIF1A expression. Cancer science 47 35848884
2021 Analysis and validation of m6A regulatory network: a novel circBACH2/has-miR-944/HNRNPC axis in breast cancer progression. Journal of translational medicine 47 34952600
2023 m6A-Modified circTET2 Interacting with HNRNPC Regulates Fatty Acid Oxidation to Promote the Proliferation of Chronic Lymphocytic Leukemia. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 46 37821382
2022 LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/β-catenin activation via interacting with hnRNPC. Journal of experimental & clinical cancer research : CR 45 36471363
2025 circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4. Molecular cancer 38 39748364
2022 LINC00924-induced fatty acid metabolic reprogramming facilitates gastric cancer peritoneal metastasis via hnRNPC-regulated alternative splicing of Mnk2. Cell death & disease 36 36418856
2019 N6-Methyladenosine detected in RNA of testicular germ cell tumors is controlled by METTL3, ALKBH5, YTHDC1/F1/F2, and HNRNPC as writers, erasers, and readers. Andrology 36 30903744
2023 HNRNPC suppresses tumor immune microenvironment by activating Treg cells promoting the progression of prostate cancer. Cancer science 30 36718950
2022 Cullin-9/p53 mediates HNRNPC degradation to inhibit erastin-induced ferroptosis and is blocked by MDM2 inhibition in colorectal cancer. Oncogene 30 35505093
2023 HNRNPC promotes collagen fiber alignment and immune evasion in breast cancer via activation of the VIRMA-mediated TFAP2A/DDR1 axis. Molecular medicine (Cambridge, Mass.) 29 37528369
2023 Circular RNA circ-FIRRE interacts with HNRNPC to promote esophageal squamous cell carcinoma progression by stabilizing GLI2 mRNA. Cancer science 28 37417427
2023 LncRNA DANCR counteracts premature ovarian insufficiency by regulating the senescence process of granulosa cells through stabilizing the interaction between p53 and hNRNPC. Journal of ovarian research 27 36805799
2022 The mechanical regulation of RNA binding protein hnRNPC in the failing heart. Science translational medicine 27 36417487
2024 TGF-β-induced lncRNA TBUR1 promotes EMT and metastasis in lung adenocarcinoma via hnRNPC-mediated GRB2 mRNA stabilization. Cancer letters 26 39102940
2022 Long non-coding RNA DDX11-AS1 promotes the proliferation and migration of glioma cells by combining with HNRNPC. Molecular therapy. Nucleic acids 26 35614994
2022 hnRNPC induces isoform shifts in miR-21-5p leading to cancer development. Experimental & molecular medicine 25 35729324
2021 ADAR and hnRNPC deficiency synergize in activating endogenous dsRNA-induced type I IFN responses. The Journal of experimental medicine 25 34297039
2022 HNRNPC regulates RhoA to induce DNA damage repair and cancer-associated fibroblast activation causing radiation resistance in pancreatic cancer. Journal of cellular and molecular medicine 24 35277915
2023 Targeting hnRNPC suppresses thyroid follicular epithelial cell apoptosis and necroptosis through m6A-modified ATF4 in autoimmune thyroid disease. Pharmacological research 21 37729957
2025 hnRNPC Functions with HuR to Regulate Alternative Splicing in an m6A-Dependent Manner and is Essential for Meiosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 19 39921484
2024 The m6A reader HNRNPC promotes glioma progression by enhancing the stability of IRAK1 mRNA through the MAPK pathway. Cell death & disease 19 38830885
2018 Friend and foe, HNRNPC takes on immunostimulatory RNAs in breast cancer cells. The EMBO journal 19 30389667
2024 Cancer-derived exosomal lncRNA SNHG3 promotes the metastasis of colorectal cancer through hnRNPC-mediating RNA stability of β-catenin. International journal of biological sciences 17 38725844
2023 HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder. American journal of human genetics 17 37541189
2012 Yeast Nab3 protein contains a self-assembly domain found in human heterogeneous nuclear ribonucleoprotein-C (hnRNP-C) that is necessary for transcription termination. The Journal of biological chemistry 17 23192344
2021 Influence of N6-Methyladenosine Modification Gene HNRNPC on Cell Phenotype in Parkinson's Disease. Parkinson's disease 15 34966539
2024 HNRNPC mediates lymphatic metastasis of cervical cancer through m6A-dependent alternative splicing of FOXM1. Cell death & disease 14 39375330
2021 Identification of HnRNPC as a novel Tau exon 10 splicing factor using RNA antisense purification mass spectrometry. RNA biology 14 34965173
2023 Case report: Identification of a novel HNRNPC::RARG fusion in acute promyelocytic leukemia lacking RARA rearrangement. Frontiers in oncology 12 36713535
2022 hnRNPC Promotes Malignancy in Pancreatic Cancer through Stabilization of IQGAP3. BioMed research international 12 35355828
2022 Serum-derived extracellular vesicles promote the growth and metastasis of non-small cell lung cancer by delivering the m6A methylation regulator HNRNPC through the regulation of DLGAP5. Journal of cancer research and clinical oncology 12 36175801
2024 HNRNPC promotes estrogen receptor-positive breast cancer cell cycle by stabilizing WDR77 mRNA in an m6A-dependent manner. Molecular carcinogenesis 11 38353359
2024 HNRNPC modulates PKM alternative splicing via m6A methylation, upregulating PKM2 expression to promote aerobic glycolysis in papillary thyroid carcinoma and drive malignant progression. Journal of translational medicine 10 39380010
2022 Circ_0022340 promotes colorectal cancer progression via HNRNPC/EBF1/SYT7 or miR-382-5p/ELK1 axis. Cellular and molecular biology (Noisy-le-Grand, France) 10 36495510
2024 Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying Circ-Tulp4 Attenuate Diabetes Mellitus with Nonalcoholic Fatty Liver Disease by Inhibiting Cell Pyroptosis through the HNRNPC/ABHD6 Axis. Tissue engineering and regenerative medicine 8 39546192
2023 N6-methylation of RNA-bound adenosine regulator HNRNPC promotes vascular endothelial dysfunction in type 2 diabetes mellitus by activating the PSEN1-mediated Notch pathway. Diabetes research and clinical practice 8 36681355
2025 HNRNPC and m6A RNA methylation control oncogenic transcription and metabolism in T-cell leukemia. Blood 7 40435411
2024 N6-Methyladenosine reader HNRNPC-mediated downregulation of circITCH prevents miR-224-3p sequestering and contributes to tumorigenesis in nasopharyngeal carcinoma. Environmental toxicology 7 38299319
2022 Identification and Validation of Three m6A Regulators: FTO, HNRNPC, and HNRNPA2B1 as Potential Biomarkers for Endometriosis. Genes 7 36672827
2023 The MYC-Regulated RNA-Binding Proteins hnRNPC and LARP1 Are Drivers of Multiple Myeloma Cell Growth and Disease Progression and Negatively Predict Patient Survival. Cancers 6 38067212
2022 Essential m6A Methylation Regulator HNRNPC Serves as a Targetable Biomarker for Papillary Renal Cell Carcinoma. Journal of oncology 6 35502201
2024 Hsa_circ_0014606 Derived from Exosomes Promotes Gastric Carcinoma Tumorigenesis and Proliferation by Sponging miR-514b-3p to Upregulate HNRNPC. Digestive diseases and sciences 5 38217675
2024 Sertoli cells require hnRNPC to support normal spermatogenesis and male fertility in mice†. Biology of reproduction 5 38590182
2024 m6A Reader HNRNPC Facilitates Adipogenesis by Regulating Cytoskeletal Remodeling through Enhanced Lcp1 mRNA Stability. Aging and disease 5 38916731
2024 Role of Circular RNA MMP9 in Glioblastoma Progression: From Interaction With hnRNPC and hnRNPA1 to Affecting the Expression of BIRC5 by Sequestering miR-149. Journal of molecular recognition : JMR 5 39401767
2022 Interaction of Influenza A Nucleoprotein with Host hnRNP-C Is Implicated in Viral Replication. International journal of molecular sciences 5 36362400
2015 Evaluating the role of hnRNP-C and FMRP in the cAMP-induced APP metabolism. BioFactors (Oxford, England) 5 25809670
2025 HNRNPC promotes progression of non-small cell lung cancer by maintaining TFAP2A mRNA stability. Cancer cell international 3 40057699
2025 The m6A reader HNRNPC is a key regulator in DSS-induced colitis by modulating macrophage phenotype. iScience 3 40124522
2025 HNRNPC stabilizes m6A-modified AC145207.5 to accelerate tumorigenesis in colorectal cancer by impeding the Nrf2/GPX4 axis-mediated ferroptosis. Non-coding RNA research 3 40290566
2025 The HNRNPC/CELF2 signaling pathway drives glycolytic reprogramming and mitochondrial dysfunction in drug-resistant acute myeloid leukemia. Cell & bioscience 3 40380235
2025 Gobal crotonylome reveals that HNRNPC and its crotonylation promote p53-deficient tumor growth by stabilizing CCND1 and MCM3 mRNAs. Cancer letters 3 40482911
2024 HNRNPC Regulates GLUT1/LDHA Pathway by Stabilizing FOXM1 mRNA to Promote the Progression and Aerobic Glycolysis of Multiple Myeloma. Annals of clinical and laboratory science 3 38514068
2024 DUSP3 modulates IRES-dependent translation of mRNAs through dephosphorylation of the HNRNPC protein in cells under genotoxic stimulus. Biology of the cell 3 38538536
2024 HNRNPC as a pan-cancer biomarker and therapeutic target involved in tumor progression and immune regulation. Oncology research 3 39735682
2022 circXRCC5 foster gastric cancer growth and metastasis by the HNRNPC/circXRCC5/miR-655-3p/RREB1/UBA2 positive feedback loop. Cancer gene therapy 3 35661832
2025 RALYL Overexpression Suppresses Colorectal Cancer via Modulating HNRNPC-Mediated MNK2 Alternative Splicing. Cancer reports (Hoboken, N.J.) 2 40052233
2025 HNRNPC-Mediated m6A Epitranscriptomics Drives CD80-Dependent Tubular Dysfunction in Sepsis-Induced AKI. Inflammation 2 41199093
2024 LncRNA LINC00173 inhibits the development of endometrial cancer by interacting with HNRNPC. Translational oncology 2 39191140
2023 HNRNPC mediated m6A methylation of 5-methyltetrahydrofolate-homocysteine methyltransferase and involved in the occurrence of RSA. Journal of reproductive immunology 2 37857158
2025 HnRNPC triggers the degradation of MITA to suppress the interferon-mediated antiviral response. Veterinary research 1 39994817
2025 Role of HNF4A-AS1/HNRNPC-mediated HNF4A ubiquitination protection against ritonavir-induced hepatotoxicity. Molecular pharmacology 1 40037142
2025 Novel RNA-methylase HNRNPC promotes gastric cancer tumorigenesis by triggering the lactate-induced ferroptosis resistance. Frontiers in immunology 1 40977716
2025 Positive Feedback Loop of Histone Lactylation-Driven HNRNPC Promotes Autophagy to Confer Pancreatic Ductal Adenocarcinoma Gemcitabine Resistance. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41309519
2025 HNRNPC reprograms cancer metabolism to drive acquired chemoresistance in colorectal cancer by repressing of Nrf2/SLC7A11-dependent ferroptosis. Cell communication and signaling : CCS 1 41366407
2024 Dysregulated inclusion of BOLA3 exon 3 promoted by HNRNPC accelerates the progression of esophageal squamous cell carcinoma. Frontiers of medicine 1 39455467
2026 [Molecular mechanism of HNRNPC mediated ferroptosis in Ang II-related coronary heart disease]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 41506875
2026 tRF-Gly-CCC-012 enhances malignant process in pancreatic cancer via the HNRNPC/PHGDH axis. Biochemical pharmacology 0 41571199
2026 Dual-targeted NIR-II AIE theranostic nanoparticles disrupt HNRNPC-driven ITGA1+ myCAFs differentiation and immune evasion in oral squamous cell carcinoma. Biomaterials 0 41702227
2026 Targeting circGDI2 disrupt HNRNPC-mediated mPORCN stabilization and enhance LGK-974 anti-tumor therapy in hepatocellular carcinoma. Molecular cancer 0 41808165
2025 The Arg99Gln Substitution in HNRNPC Is Associated with a Distinctive Clinical Phenotype Characterized by Facial Dysmorphism and Ocular and Cochlear Anomalies. Genes 0 40004505
2025 HNRNPC Promotes Keloid Progression by Modulating the Stability of N6-Methyladenosine-Modified WDR77 mRNA and Expression of TGF-β and SMAD3. The Journal of investigative dermatology 0 40484365
2025 Long Noncoding RNA CCDC26 Interacts With Vimentin, HNRNPC, CBX1, and CBX5 Proteins in Multiple Intracellular Compartments of Myeloid Leukemia Cells. Genes to cells : devoted to molecular & cellular mechanisms 0 40518278
2025 HNRNPC aggravates the symptoms of preeclampsia by regulating m6A-dependent alternative splicing of ACSL3. Journal of hypertension 0 41037014
2025 HHIPL2 positively governs Hedgehog signaling to accelerate non-small cell lung cancer progression via enhancing HNRNPC-mediated HNF1A mRNA stabilization. Cell death & disease 0 41413056
2025 Unveiling the ZNF384-INTS13-hnRNPC axis as a therapeutic vulnerability in cervical cancer. Cell death & disease 0 41429980
2025 Clinical and Pathologic Description of Three Aneurysmal Bone Cyst Cases With Novel USP6 Fusion Partners Including SEC24D, HNRNPC, and ERRFI1. Genes, chromosomes & cancer 0 41432301
2025 HNRNPC lactylation promotes pancreatic cancer progression through mediating the alternative splicing of PAK6. Cancer letters 0 41435694
2022 Construction and clinical evaluation of N6-methyladenosine risk signature of YTHDC2, IGF2BP2, and HNRNPC in head and neck squamous cell carcinoma. Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology 0 36416324