ArticleResearch (Washington, D.C.)2025
PRMT5-Mediated ALKBH5 Methylation Promotes Colorectal Cancer Immune Evasion via Increasing CD276 Expression.
Article in Research (Washington, D.C.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
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Who cites it
23 citing papers in PubMed.
- Glutamine transporter SLC1A5 inhibits autophagy-mediated CD276 degradation to promote esophageal cancer progression.Cancer biology & therapy · 2026Article
- Protein arginine methylation and ubiquitination: A prominent crosstalk and its functions in cancer.Genes & diseases · 2026Review
- CD276 promotes lipid metabolic reprogramming and regulates ferroptosis in clear cell renal cell carcinoma by upregulating FASN expression via SREBP1.Human cell · 2026Article
- RNA Metabolism Genes as Prognostic Biomarkers and Therapeutic Targets in Colorectal Cancer Based on the Analysis of Single-Cell and Bulk-RNA Sequencing Data.Journal of cellular and molecular medicine · 2026Article
- Emerging role of protein arginine methyltransferase 5 in gastrointestinal cancer (Review).Oncology letters · 2026Review
- TRIM28 orchestrates SUMO-ubiquitin crosstalk to stabilize PPARG and drive bladder cancer progression.Cell death & disease · 2026Article
- Emerging Dual Roles of ALKBH5 in Ischemia-reperfusion Injury: Mechanisms and Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- RNA Regulatory Networks: Key Hubs in the Panorama of Cancer and Emerging Therapeutic Targets.MedComm · 2026Review
- REEP6 promotes colorectal cancer glycolysis and tumorigenesis through PRMT5-mediated PGAM1 arginine methylation.Acta pharmaceutica Sinica. B · 2026Article
- Glycolysis-mediated H3K18la modifications drive aggressive bladder cancer through metabolic and epigenetic reprogramming.Frontiers in immunology · 2026Article
- Integrated CT Foundation Model and Radiomic Features Define Clinically and Biologically Distinct Colorectal Cancer Subtypes.Research (Washington, D.C.) · 2026Article
- NResearch (Washington, D.C.) · 2026Article
- Biofunctional Pectin Derived from Pomelo Peel: Structural Insights and Neuro-Gut Protective Mechanisms in Zebrafish under Bisphenol AF-Induced Neurotoxicity.Research (Washington, D.C.) · 2026Article
- Context-dependent functions of ALKBH5: a mechanistic framework linking cellular stress responses, immune regulation, viral infection, and therapeutic vulnerabilities.Frontiers in immunology · 2026Review
- Bidirectional regulation of the ubiquitin-RNA modification axis in cancer.Frontiers in oncology · 2026Review
- Protein arginine methyltransferase 7-mediated arginine mono-methylation stabilizes SRY-box transcription factor 9 to promote non-small cell lung cancer progression.Molecular biomedicine · 2025Article
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- The mMolecular biomedicine · 2025Review
- Arginine methylation patterns in LUAD: defining prognostic subtypes and relevance to immunotherapy.Discover oncology · 2025Article
- CBX4 Drives Gastric Cancer Progression by ActivatingOncology research · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous diseases have been connected to protein arginine methylations mediated by protein arginine methyltransferase 5 (PRMT5). Clinical investigations of the PRMT5-specific inhibitor GSK3326595 are currently being conducted, and the results are promising for preventing cancers. However, the detailed mechanism of PRMT5 promoting colorectal cancer (CRC) malignant progression remains unclear. Here, we found that PRMT5 directly catalyzes AlkB homologue 5 (ALKBH5) symmetric dimethylation at the R316 residue (meR316-ALKBH5), which enhances TRIM28-mediated ALKBH5 ubiquitination degradation. Then, an ALKBH5 decrease attenuates ALKBH5-mediated m6A demethylation on the CD276 transcript 3' untranslated region, which increases CD276 messenger RNA stability and its expression in CRC cells. Furthermore, a CD276 expression increase facilitates CRC immune evasion by inhibiting cytotoxic T-cell functions. Moreover, we revealed that PRMT5-mediated meR316-ALKBH5 activates CD276 transcription by increasing its messenger RNA m6A modification to increase CRC immune evasion in vitro and in vivo. Furthermore, we consistently showed a strong association between meR316-ALKBH5 and poor outcomes in patients with CRC. Finally, we demonstrated that combining an anti-PD1 antibody with the PRMT5 inhibitor GSK3326595 markedly halts the progression of CRC. Our findings could serve as a basis for the development of a PRMT5-meR316-ALKBH5-CD276 axis-targeting treatment approach for CRC.
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Registered trials
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