Abstract
N6-methyladenosine (m6A) modification is the most common chemical modification in eukaryotic mRNA, which plays a crucial role in regulating mRNA stability, splicing, and translation. METTL3 (methyltransferase like 3), a major RNA N6-adenosine methyltransferase, has been reported to participate in the progression of many cancers. However, its function in colorectal cancer (CRC) remains largely unknown. In this study, we revealed that METTL3 played an oncogenic role in CRC. We found that METTL3 was significantly upregulated in CRC, using quantitative real-time PCR, western blotting, and immunohistochemical staining, and upregulation of METTL3 was associated with clinicopathological features. Functionally, knockdown of METTL3 suppressed CRC cell proliferation in vitro and in vivo. In contrast, overexpression of METTL3 promoted the growth of CRC cells both in vitro and in vivo. Mechanistically, METTL3 exerted its function through enhancing MYC expression, at least partially in an m6A-IGF2BP1-dependent manner. In conclusion, we found that METTL3 was frequently upregulated in human CRC and promoted CRC progression though enhancing MYC expression. This provided new insights into the molecular mechanisms underlying the development of colorectal cancer.