tsRNA-10547 generated by m1A modification-mediated tRNA shearing promotes colorectal cancer metastasis by suppressing CHRNA9 via AGO2 binding

tRNA-derived fragments (tsRNAs) have been identified as playing a critical role in tumor processes; however, the function of tsRNAs in regulating colorectal cancer (CRC) metastasis remains largely unexplored. tsRNA-10547 was identified by bioinformatics analysis and validated using clinical samples. RNA-seq was employed to identify the target gene CHRNA9 of tsRNA-10547. The expression levels of tsRNA-10547, CHRNA9, and TRMT10C were quantified using qRT-PCR, CCK8, scratch healing, and transwell. Western blot, fluorescence in situ hybridization, and RNA pull-down assays were performed to verify protein expression and interactions. tsRNA-10547 was significantly upregulated in both CRC cells and clinical samples, promoting the invasion and migration of CRC cells. In vivo, the mice in the tsRNA-10547 mimics group exhibited pronounced tumor metastasis. Additionally, the m1A-modification enzyme TRMT10C was upregulated in CRC clinical samples, tsRNA-10547-derived tRNA-Arg-TCT was significantly enriched in m1A-modified cells. Mechanistically, tsRNA-10547 suppresses CHRNA9 expression by binding to the Argonaute 2 (AGO2) protein in CRC. Our study systematically elucidated the mechanism by which tsRNA-10547, dependent on m1A-modified tRNA cleavage, promotes CRC metastasis by suppressing CHRNA9 via AGO2 protein binding. These findings provide valuable insights for the prevention and treatment of CRC metastasis and contribute to the clinical translation of tsRNA function.