Extracellular Vesicle-Packaged circTAX1BP1 from Cancer-Associated Fibroblasts Regulates RNA m6A Modification through Lactylation of VIRMA in Colorectal Cancer Cells.

ABSTRACT: The underlying molecular mechanism of patients with colorectal liver metastasis (CRLM) remains unclear. In this study, it is found that cancer-associated fibroblasts (CAFs)-derived extracellular vesicles (EVs) are significantly enriched in circTAX1BP1 in CRLM, which associate with poor prognosis. The disruption of EV-packaged circTAX1BP1 significantly inhibits CRLM in vivo and in vitro. Mechanistically, CAF-derived EV-packaged circTAX1BP1 is delivered to colorectal cancer (CRC) cells, where it binds to VIRMA and promotes its lactylation at lysine residue 1713 by recruiting AARS2. Lactylated VIRMA enhances m⁶A-based modification and stability of SP1 mRNA. SP1 mediates the transcription of TGF-β, enhancing epithelial-mesenchymal transition and paracrine TGF-β of CRC cells. Notably

SUBMITTER: Tan JN 

PROVIDER: S-EPMC12713077 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature