Methyltransferase like 3 promotes colorectal cancer proliferation by stabilizing CCNE1 mRNA in an m6A-dependent manner |
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| Authors: | Wei Zhu Yan Si Jun Xu Yu Lin Jing-Zi Wang Mengda Cao Shanwen Sun Qiang Ding Lingjun Zhu Ji-Fu Wei |
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| Institution: | 1. Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing, China;2. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing, China;3. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing, China;4. Department of Urology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing, China |
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| Abstract: | 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. |
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| Keywords: | butyrate CCNE1 colorectal cancer intestinal microbiota metabolites m6A methyltransferase like 3 |
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