ArticleNucleic acids research2017
hnRNPM guides an alternative splicing program in response to inhibition of the PI3K/AKT/mTOR pathway in Ewing sarcoma cells.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 79 citations in OpenAlex.
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- CircSPARC promotes esophageal squamous cell carcinoma through an HNRNPC-EPN2 splicing axis that activates Wnt/β-Catenin signaling.Molecular cancer · 2026Article
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
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- A Dual Approach with Organoid and CRISPR Screening Reveals ERCC6 as a Determinant of Cisplatin Resistance in Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Super-enhancer-driven EFNA1 fuels tumor progression in cervical cancer via the FOSL2-Src/AKT/STAT3 axis.The Journal of clinical investigation · 2025Article
- DHX9 helicase impacts on splicing decisions by modulating U2 snRNP recruitment in Ewing sarcoma cells.Nucleic acids research · 2025Article
- HnRNPM modulates alternative splicing in germ cells by recruiting PTBP1.Reproductive biology and endocrinology : RB&E · 2025Article
- Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.Research (Washington, D.C.) · 2025Review
- Nutrient control of growth and metabolism through mTORC1 regulation of mRNA splicing.Molecular cell · 2024Article
- PARP4 interacts with hnRNPM to regulate splicing during lung cancer progression.Genome medicine · 2024Article
- The bovine leukemia virus-derived long non-coding RNA AS1-S binds to bovine hnRNPM and alters the interaction between hnRNPM and host mRNAs.Microbiology spectrum · 2023Article
- Identification of KIFC1 as an independent prognostic marker in renal clear cell carcinoma correlates with tumor proliferation and immune infiltration.Scientific reports · 2023Article
- Polyadenylate-binding protein cytoplasmic 1 mediates alternative splicing events of immune-related genes in gastric cancer cells.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- mTOR Contributes to the Proteome Diversity through Transcriptome-Wide Alternative Splicing.International journal of molecular sciences · 2022Article
- Downregulation of HNRNPM inhibits cell proliferation and migration of hepatocellular carcinoma through MAPK/AKT signaling pathway.Translational cancer research · 2022Article
- The Oncogenic PI3K-Induced Transcriptomic Landscape Reveals Key Functions in Splicing and Gene Expression Regulation.Cancer research · 2022Article
- The DNA/RNA helicase DHX9 contributes to the transcriptional program of the androgen receptor in prostate cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ewing sarcomas (ES) are biologically aggressive tumors of bone and soft tissues for which no cure is currently available. Most ES patients do not respond to chemotherapeutic treatments or acquire resistance. Since the PI3K/AKT/mTOR axis is often deregulated in ES, its inhibition offers therapeutic perspective for these aggressive tumors. Herein, by using splicing sensitive arrays, we have uncovered an extensive splicing program activated upon inhibition of the PI3K/AKT/mTOR signaling pathway by BEZ235. Bioinformatics analyses identified hnRNPM as a key factor in this response. HnRNPM motifs were significantly enriched in introns flanking the regulated exons and proximity of binding represented a key determinant for hnRNPM-dependent splicing regulation. Knockdown of hnRNPM expression abolished a subset of BEZ235-induced splicing changes that contained hnRNPM binding sites, enhanced BEZ235 cytotoxicity and limited the clonogenicity of ES cells. Importantly, hnRNPM up-regulation correlates with poor outcome in sarcoma patients. These findings uncover an hnRNPM-dependent alternative splicing program set in motion by inhibition of the mTOR/AKT/PI3K pathway in ES cells that limits therapeutic efficacy of pharmacologic inhibitors, suggesting that combined inhibition of the PI3K/AKT/mTOR pathway and hnRNPM activity may represent a novel approach for ES treatment.
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