A novel tRNA-derived fragment, tRF-16-WSNKP9D promotes malignant progression of colorectal carcinoma through mediating PFN1.

Although transfer RNA-derived fragments (tRFs) regulate oncogenesis, their specific functions in colorectal carcinoma (CRC) remain unclear. Using RNA sequencing, we identified a novel fragment, tRF-16-WSNKP9D, significantly upregulated in CRC tissues. Clinically, high tRF-16-WSNKP9D levels strongly correlated with poor patient survival and showed potential in distinguishing tumor from normal tissues. Functional assays revealed that silencing tRF-16-WSNKP9D impaired CRC cell proliferation, clonogenicity, and migration, while triggering apoptosis in vitro and suppressing xenograft tumor growth in vivo. Mechanistically, tRF-16-WSNKP9D directly targets and downregulates profilin 1 (PFN1). Depleting this tRF restored PFN1 expression, effectively neutralizing the induced malignant phenotypes. Ultimately, our study establishes that tRF-16-WSNKP9D drives CRC progression by impairing PFN1-mediated tumor suppression. These findings highlight this novel RNA molecule as a potential therapeutic target and a candidate biomarker for CRC prognosis.