ArticleJournal of neuro-oncology2019
The protein arginine methyltransferase PRMT5 confers therapeutic resistance to mTOR inhibition in glioblastoma.
Article in Journal of neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 56 citations in OpenAlex.
- PRMT5 as a Key Driver of Stemness and Metastatic Potential in Triple-Negative Breast Cancer.Biomolecules · 2026Review
- PKA signaling modulates PRMT5/hnRNP A1-mediated IRES translation and dictates responses to mTOR inhibition in glioblastoma.Journal of neuro-oncology · 2026Article
- Protein Arginine Methyltransferases in γ-Globin Regulation and Sickle Cell Disease: Emerging Connections to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2026Review
- Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.Experimental hematology & oncology · 2026Review
- Review
- PRMT5 upregulates KCNMB4 expression via histone methylation to promote paclitaxel resistance in advanced nasopharyngeal carcinoma.Cell death & disease · 2026Article
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- Exploiting Synthetic Lethality of PRMT5 for Precision Treatment of MTAP-Deficient Glioblastoma.International journal of translational medicine (Basel, Switzerland) · 2025Article
- PRMT5 Inhibition as a Potential Strategy for KRAS Mutant CRC: Downstream Mediators of the PRMT5-KRAS Crosstalk.Current issues in molecular biology · 2025Article
- Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights.Biomarker research · 2025Review
- Protein Arginine Methyltransferases from Regulatory Function to Clinical Implication in Central Nervous System.Cellular and molecular neurobiology · 2025Review
- The epigenetic mechanisms involved in the treatment resistance of glioblastoma.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- PRMT5 Inhibitor EPZ015666 Decreases the Viability and Encystment ofMolecules (Basel, Switzerland) · 2024Article
- Regulation of HNRNP family by post-translational modifications in cancer.Cell death discovery · 2024Review
- Resistance to PRMT5-targeted therapy in mantle cell lymphoma.Blood advances · 2024Article
- Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance.Frontiers in molecular biosciences · 2024Review
- Review
- Critical Roles of Protein Arginine Methylation in the Central Nervous System.Molecular neurobiology · 2023Review
- mCancer letters · 2023Article
- Therapeutic Advantage of Targeting PRMT5 in Combination with Chemotherapies or EGFR/HER2 Inhibitors in Triple-Negative Breast Cancers.Breast cancer (Dove Medical Press) · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
introductionClinical trials directed at mechanistic target of rapamycin (mTOR) inhibition have yielded disappointing results in glioblastoma (GBM). A major mechanism of resistance involves the activation of a salvage pathway stimulating internal ribosome entry site (IRES)-mediated protein synthesis. PRMT5 activity has been implicated in the enhancement of IRES activity.
methodsWe analyzed the expression and activity of PRMT5 in response to mTOR inhibition in GBM cell lines and short-term patient cultures. To determine whether PRMT5 conferred resistance we used genetic and pharmacological approaches to ablate PRMT5 activity and assessed the effects on in vitro and in vivo sensitivity. Mutational analyses of the requisite IRES-trans-acting factor (ITAF), hnRNP A1 determined whether PRMT5-mediated methylation was necessary for ITAF RNA binding and IRES activity.
resultsPRMT5 activity is stimulated in response to mTOR inhibitors. Knockdown or treatment with a PRMT5 inhibitor blocked IRES activity and sensitizes GBM cells. Ectopic expression of non-methylatable hnRNP A1 mutants demonstrated that methylation of either arginine residues 218 or 225 was sufficient to maintain IRES binding and hnRNP A1-dependent cyclin D1 or c-MYC IRES activity, however a double R218K/R225K mutant was unable to do so. The PRMT5 inhibitor EPZ015666 displayed synergistic anti-GBM effects in vitro and in a xenograft mouse model in combination with PP242.
conclusionsThese results demonstrate that PRMT5 activity is stimulated upon mTOR inhibition in GBM. Our data further support a signaling cascade in which PRMT5-mediated methylation of hnRNP A1 promotes IRES RNA binding and activation of IRES-mediated protein synthesis and resultant mTOR inhibitor resistance.
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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.