ArticleNature communications2025
hnRNPL phase separation activates PIK3CB transcription and promotes glycolysis in ovarian cancer.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Transfer RNA-Derived Small RNA-5'tiRNAGln Drives HNRNPC Phase Separation to Promote Breast Cancer Bone Metastasis by Regulating IGF1R.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- BMAL1 regulates circadian rhythms via phase separation-mediated transcriptional hub formation.Signal transduction and targeted therapy · 2026Article
- Liquid-liquid phase separation in cancer therapy resistance.iScience · 2026Review
- MEX3B aggravates osteoarthritis progression by post-transcriptionally activating TLR4-NF-κB signaling axis.Journal of orthopaedic surgery and research · 2026Article
- Integrative multi-omics analysis identifies SNRPE as a key driver gene in uterine corpus endometrial carcinoma: promoting tumor progression, and mediating immune evasion.Frontiers in immunology · 2026Article
- hnRNPL-CstF64 complex: coordinating CSR and LSR in IgH locus recombination dynamics through eRNA and NHEJ regulation.Nucleic acids research · 2025Article
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Authors and funding
20 authors.
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Abstract
Ovarian cancer has the highest mortality rate among gynecologic tumors worldwide, with unclear underlying mechanisms of pathogenesis. RNA-binding proteins (RBPs) primarily direct post-transcriptional regulation through modulating RNA metabolism. Recent evidence demonstrates that RBPs are also implicated in transcriptional control. However, the role and mechanism of RBP-mediated transcriptional regulation in tumorigenesis remain largely unexplored. Here, we show that the RBP heterogeneous ribonucleoprotein L (hnRNPL) interacts with chromatin and regulates gene transcription by forming phase-separated condensates in ovarian cancer. hnRNPL phase separation activates PIK3CB transcription and glycolysis, thus promoting ovarian cancer progression. Notably, we observe that the PIK3CB promoter is transcribed to produce a non-coding RNA which interacts with hnRNPL and promotes hnRNPL condensation. Furthermore, hnRNPL is significantly amplified in ovarian cancer, and its high expression predicts poor prognosis for ovarian cancer patients. By using cell-derived xenograft and patient-derived organoid models, we show that hnRNPL knockdown suppresses ovarian tumorigenesis. Together, our study reveals that phase separation of the chromatin-associated RBP hnRNPL promotes PIK3CB transcription and glycolysis to facilitate tumorigenesis in ovarian cancer. The formed hnRNPL-PIK3CB-AKT axis depending on phase separation can serve as a potential therapeutic target for ovarian cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.