WTAP/IGF2BP3 Mediated m6A Modification of SOD2 mRNA Aggravates the Tumourigenesis of Colorectal Cancer

Wilms tumor 1-associated protein (WTAP) has been validated to be a crucial regulator in the tumorigenesis and advancement of diverse malignancies. This study intended to probe the impacts of WTAP on colorectal cancer (CRC) progression from the perspective of N6-methyladenosine (m6A) modification. The differential expression patterns of WTAP in clinical CRC samples and cultured cell lines were validated via qRT-PCR and western blot. Cell function tests were conducted with colony formation, transwell, and CCK-8. MeRIP-qPCR was conducted to identify the WTAP-mediated SOD2 (Superoxide dismutase 2) mRNA modification in CRC cells. Animal experiments were adopted to evaluate the function of WTAP in vivo. WTAP exhibited high expression pattern in CRC samples along with cells. Silencing of WTAP potently restrained the growth of CRC tumorigenesis in virto and in vivo. Mechanically, SOD2 was identified as an m6A target of WTAP. WTAP-mediated m6A modification of SOD2 mRNA elevated its stability in an IGF2BP3-dependent manner. Meanwhile, SOD2 overexpression could reverse the tumor suppressive effect induced by WTAP silencing. Molecular therapy targeting WTAP-SOD2 may offer novel insights and perspectives for the treatment of CRC.