ArticleJournal of translational medicine2024
METTL1 mediates PKM m7G modification to regulate CD155 expression and promote immune evasion in colorectal cancer.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- GnRH Promotes Gonadotropin Synthesis and Secretion in the Bovine Anterior Pituitary by Inhibiting METTL1-Mediated m7G Modification of FOXO1 mRNA.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Understanding the epigenetic regulation of lactylation and aberrant lactate metabolism in cancer: From mechanisms to therapeutic strategies (Review).International journal of oncology · 2026Review
- Beyond a Metabolite: Lactylation as a Pivotal Regulator of Colorectal Cancer Pathogenesis and Treatment Resistance.Journal of biochemical and molecular toxicology · 2026Review
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- Clinical implications of lactylation modification in digestive system tumors (Review).Oncology letters · 2026Review
- Transcriptomic identification of key genes influencing m7G modification in thyroid carcinoma and experimental validation.Discover oncology · 2026Article
- N7-Methylguanosine Modification in Colorectal Cancer: Molecular Insights and Clinical Implications.International journal of molecular sciences · 2026Review
- Lactylation in Colorectal Cancer: Regulatory Networks, Functional Mechanisms, and Clinical Translational Potential.International journal of molecular sciences · 2026Review
- Lactate metabolic reprogramming and lactylation modification: molecular mechanisms reshaping the tumor immunosuppressive microenvironment.Cell & bioscience · 2026Review
- Lactate metabolism-driven lactylation: paradoxical modulation of intestinal inflammation and malignancy.Journal of translational medicine · 2026Review
- RNA modification-mediated multidimensional crosstalk: a novel perspective on gene expression regulation.Genome biology · 2026Review
- Article
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- METTL1-mediated mCellular oncology (Dordrecht, Netherlands) · 2026Article
- Glycolysis enzymes and cellular lactylation in tumour.Clinical and translational medicine · 2026Review
- Advances in research on RNA methylation and its role in the immune microenvironment of gastrointestinal tumors.Frontiers in cell and developmental biology · 2026Review
- RNA epitranscriptomic regulation of tumor immune evasion: mechanisms, context-dependent roles, and therapeutic implications.Frontiers in immunology · 2026Review
- RNA Methylation in Cancer Metabolism: from Mechanisms to Therapeutic Opportunities.International journal of biological sciences · 2026Review
- Lactylation in urological malignancies: emerging mechanisms and therapeutic direction.Frontiers in cell and developmental biology · 2026Review
- Histone lactylation in gastrointestinal cancers: developing immunotherapeutic drugs targeting epigenetics.Archives of pharmacal research · 2025Review
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12 authors.
Funding
Abstract
backgroundColorectal cancer (CRC) is characterized by poor responsiveness to immune evasion and immunotherapy. RNA 7-methylguanine (m7G) modification plays a key role in tumorigenesis. However, the mechanisms by which m7G-modified RNA metabolism affects tumor progression are not fully understood, nor is the contribution of m7G-modified RNA to the CRC immune microenvironment.
methodsThe expression levels of Methyltransferase-like 1 (METTL1) and m7G in human tissues were determined. In this study, the effect of METTL1 on RNA m7G levels was evaluated, the effect of METTL1 on PKM mRNA modification was confirmed, the expression level of the PKM2 protein was detected, and the mechanism involved RT‒qPCR, Western blot, RNA stability analysis and RIP analysis. Lactate and H3K9 lactylation (H3K9la) induced by METTL1/PKM2 were analyzed via the extracellular acidification rate (ECAR) and lactic acid assays. Cut&Run was used to detect METTL1/PKM2-induced CD155 (PVR) transcription. In addition, METTL1 knockout mice were studied in vivo with CD155 blockers.
resultsWe demonstrated that m7G RNA METTL1 enhances PKM2 expression by acting on PKM mRNA, leading to tumor progression and increased glycolysis. Specifically, METTL1 mediates m7G methylation of PKM mRNA and enhances the expression of its encoded PKM2, which in turn enhances glycolysis, promotes H3K9la, and activates METTL1 transcription, creating a positive feedback loop. Moreover, increased PKM2 dimer expression and nuclear translocation activated CD155 expression and induced CRC immune evasion.
conclusionsOur findings reveal a general mechanism by which METTL1/PKM2/H3K9la signaling regulates RNA metabolism and highlight METTL1 targeting as a potential strategy for CRC immunotherapy.
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