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RNA m1A methyltransferase TRMT61A induces MAPK/ERK signaling and is a therapeutic target in colorectal cancer I

GSE274027 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2025/02/01 Platform GPL24676
Summary
The role of N1-methyladenosine (m1A) in cancer remains poorly understood. Here we investigate the functional importance of RNA m1A methyltransferase TRMT61A in colorectal cancer (CRC) and assess its potential as a therapeutic target. Our findings demonstrate consistent elevation of TRMT61A expression and RNA m1A levels in primary CRC tissues, which correlate significantly with poor patient survival. Through CRISPR/Cas9 screenings, TRMT61A is the most essential gene among m1A regulators. We further elucidate that TRMT61A facilitates CRC tumorigenesis and progression by enhancing the stability of mRNA of crucial targets, including ONECUT2, thereby activating the MAPK/ERK signaling pathway in an m1A-dependent manner. Of note, we show promising anti-CRC effects by inhibiting TRMT61A using nanoparticleencapsulated siTRMT61A or our identified small molecule compound, PGG. Collectively, our study uncovers the essential role of TRMT61A-m1A in CRC by activating the ONECUT2-MAPK/ERK pathway. Targeting TRMT61A holds promise as a therapeutic approach for treating CRC.
Published in
RNA m(1)A methyltransferase TRMT61A promotes colorectal tumorigenesis by enhancing ONECUT2 mRNA stability and is a potential therapeutic target
Zhang X, Qin N, Ji F et al. · Cancer communications (London, England) 2025 · PMID 41103012 · doi:10.1002/cac2.70070
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Also filed as BioProject PRJNA1144485 and SRA study SRP524666. Searching any of these in the dataset finder brings you back here.

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