Methyltransferase like 3 promotes colorectal cancer proliferation by stabilizing CCNE1 mRNA in an m6A‐dependent manner

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 6; pp. 3521 - 3533
• Main Authors: Zhu, Wei, Si, Yan, Xu, Jun, Lin, Yu, Wang, Jing‐Zi, Cao, Mengda, Sun, Shanwen, Ding, Qiang, Zhu, Lingjun, Wei, Ji‐Fu
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.03.2020; John Wiley and Sons Inc
• Subjects: 3' Untranslated regions; butyrate; CCNE1; Cell cycle; Cell growth; Cell proliferation; Colorectal cancer; Colorectal carcinoma; Epigenetics; Gene expression; intestinal microbiota metabolites; Intestine; Kidney cancer; Laboratory animals; Leukemia; m6A; Metabolites; Methyltransferase; methyltransferase like 3; Microbiota; mRNA; N6-methyladenosine; Original; Proteins; RNA modification; Stem cells; Studies; Tumors; m6A; colorectal cancer; butyrate; CCNE1; intestinal microbiota metabolites; methyltransferase like 3
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.15042

m6A modification is the most prevalent RNA modification in eukaryotes. As the critical N6‐methyladenosine (m6A) methyltransferase, the roles of methyltransferase like 3 (METTL3) in colorectal cancer (CRC) are controversial. Here, we confirmed that METTL3, a critical m6A methyltransferase, could facilitate CRC progression in vitro and in vivo. Further, we found METTL3 promoted CRC cell proliferation by methylating the m6A site in 3′‐untranslated region (UTR) of CCNE1 mRNA to stabilize it. Moreover, we found butyrate, a classical intestinal microbial metabolite, could down‐regulate the expression of METTL3 and related cyclin E1 to inhibit CRC development. METTL3 promotes CRC proliferation by stabilizing CCNE1 mRNA in an m6A‐dependent manner, representing a promising therapeutic strategy for the treatment of CRC.