m6A-Modulated RNF14 Favors Fatty Acid Oxidation to Drive Colorectal Cancer Progression via Regulation of TAF1/PINK1 Axis.

The contribution of fatty acid oxidation (FAO) to colorectal cancer (CRC) progression has been recognized. However, the detailed mechanisms underlying FAO remain obscure. This study explored the influence of ring finger protein 14 (RNF14) on FAO and its related mechanisms in CRC. We found that RNF14 was up-regulated in CRC, which was positively associated with FAO level. High expression of RNF14 promoted FAO to facilitate growth of CRC cells in vitro and in vivo. Mechanistically, RNA binding motif protein 15 (RBM15)/YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-mediated N6-methyladenosine (m6A) modification enhanced RNF14 translation. RNF14 reduced TATA-box binding protein associated factor 1 (TAF1) protein stability via promoting its ubiquitination. Moreover, TAF1 bound to PTEN-induced kinase 1 (PINK1) promoter to trigger its transcription. RNF14 knockdown or TAF1 overexpression repressed FAO of CRC cells, which was overturned by TAF1 or PINK1 silencing, respectively. In conclusion, RBM15/YTHDF1-mediated m6A modification of RNF14 mRNA contributed to FAO enhancement via ubiquitination of TAF1 to transcriptionally inhibit PINK1, thus promoting CRC progression.