ArticleProceedings of the National Academy of Sciences of the United States of America2023
The RNA-binding proteins hnRNP H and F regulate splicing of a MYC-dependent HRAS exon in prostate cancer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 31 citations in OpenAlex.
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- Review
- Review
- Nucleic Acid Therapeutics for "Undruggable" Cancer Targets: Mechanisms, Challenges, and Prospects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- HNRNPF Increases MAF and CCNB2 Levels To Promote Cancer Cell Stemness and Progression of Pancreatic Ductal Adenocarcinoma.Stem cell reviews and reports · 2026Article
- HNRNPH1 drives glioblastoma progression by regulating the splicing of cell cycle genes.Cell death & disease · 2026Article
- The human branchpoint-interacting stem-loop sequence and structure regulates U2 snRNA expression, branchpoint recognition, and the transcriptome.Nucleic acids research · 2026Article
- RNA G-quadruplexes mediate cooperativity in HNRNPH binding and splicing regulation.bioRxiv : the preprint server for biology · 2026Article
- Mechanistic insights and clinical implications of RNA-binding proteins in prostate cancer.Discover oncology · 2026Review
- Inhibition of the U12-type splicing factor ZCRB1 mediates retention of the USP21 minor intron to suppress malignant progression in hepatocellular carcinoma.Hepatology international · 2026Article
- The emerging role of mFrontiers in immunology · 2026Review
- Nanotechnology in Prostate Cancer: PSMA-Targeted Nanoplatforms, TME-Responsive Therapy, Immunomodulation, and Clinical Translation Challenges.International journal of nanomedicine · 2026Review
- Identification and functional characterization of splicing factors implicated in mantle cell lymphoma aggressiveness.Scientific reports · 2025Article
- Unraveling the impact of VHL exon 2 mutations in erythrocytosis or von Hippel-Lindau disease identified RNA-binding proteins involved in VHL splicing.American journal of human genetics · 2025Article
- KATMAP infers splicing factor activity and regulatory targets from knockdown data.Nature biotechnology · 2025Article
- Role of Advanced Glycation End Products and Mitohormesis in Cancer Development and Progression.Antioxidants (Basel, Switzerland) · 2025Review
- The human branchpoint-interacting stem loop sequence and structure regulates U2 snRNA expression, branchpoint recognition, and transcriptome.bioRxiv : the preprint server for biology · 2025Article
- Emerging implications of N6-methyladenosine in prostate cancer progression and treatment.Cell death discovery · 2025Review
- HNRNPH1-mediated splicing events regulatebioRxiv : the preprint server for biology · 2025Article
- hnRNPH1: A Multifaceted Regulator in RNA Processing and Disease Pathogenesis.International journal of molecular sciences · 2025Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The MYC proto-oncogene contributes to the pathogenesis of more than half of human cancers. Malignant transformation by MYC transcriptionally up-regulates the core pre-mRNA splicing machinery and causes misregulation of alternative splicing. However, our understanding of how splicing changes are directed by MYC is limited. We performed a signaling pathway-guided splicing analysis to identify MYC-dependent splicing events. These included an HRAS cassette exon repressed by MYC across multiple tumor types. To molecularly dissect the regulation of this HRAS exon, we used antisense oligonucleotide tiling to identify splicing enhancers and silencers in its flanking introns. RNA-binding motif prediction indicated multiple binding sites for hnRNP H and hnRNP F within these cis-regulatory elements. Using siRNA knockdown and cDNA expression, we found that both hnRNP H and F activate the HRAS cassette exon. Mutagenesis and targeted RNA immunoprecipitation implicate two downstream G-rich elements in this splicing activation. Analyses of ENCODE RNA-seq datasets confirmed hnRNP H regulation of HRAS splicing. Analyses of RNA-seq datasets across multiple cancers showed a negative correlation of HNRNPH gene expression with MYC hallmark enrichment, consistent with the effect of hnRNP H on HRAS splicing. Interestingly, HNRNPF expression showed a positive correlation with MYC hallmarks and thus was not consistent with the observed effects of hnRNP F. Loss of hnRNP H/F altered cell cycle progression and induced apoptosis in the PC3 prostate cancer cell line. Collectively, our results reveal mechanisms for MYC-dependent regulation of splicing and point to possible therapeutic targets in prostate cancers.
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