Roles of METTL3 in cancer: mechanisms and therapeutic targeting

• Published in: Journal of hematology and oncology 2020-08, Vol.13 (1), p.117-15, Article 117
• Main Authors: Zeng, Chengwu, Huang, Wanxu, Li, Yangqiu, Weng, Hengyou
• Format: Article
• Language: English
• Subjects: Adenosine - analogs & derivatives; Adenosine - metabolism; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Binding, Competitive; Cancer; Cancer treatment; Carcinogens; Cell growth; Drug Design; Drug discovery; Drug Screening Assays, Antitumor; Gene Expression Regulation, Neoplastic; Growth factors; Health aspects; Hematology; Humans; Leukemia; Liver cancer; m6A; Methylation; Methyltransferases - antagonists & inhibitors; Methyltransferases - chemistry; Methyltransferases - genetics; Methyltransferases - physiology; METTL3; MicroRNAs; Models, Molecular; Molecular modelling; Molecular Targeted Therapy; mRNA; N6-methyladenosine; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - chemistry; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - therapy; NMR; Non-coding RNA; Nuclear magnetic resonance; Oncogenes; Oncology; Protein Conformation; Protein Domains; Protein structure; Proteins; Recombinant Fusion Proteins - pharmacology; Recombinant Fusion Proteins - therapeutic use; Recruitment; Regulation; Review; RNA; RNA modification; RNA Processing, Post-Transcriptional; RNA, Neoplasm - metabolism; Substrate Specificity; Therapeutic targets; Transferases; Tumor Suppressor Proteins - antagonists & inhibitors; Tumor Suppressor Proteins - chemistry; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - physiology
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-020-00951-w

N -methyladenosine (m A) is the most abundant mRNA modification and is catalyzed by the methyltransferase complex, in which methyltransferase-like 3 (METTL3) is the sole catalytic subunit. Accumulating evidence in recent years reveals that METTL3 plays key roles in a variety of cancer types, either dependent or independent on its m A RNA methyltransferase activity. While the roles of m A modifications in cancer have been extensively reviewed elsewhere, the critical functions of METTL3 in various types of cancer, as well as the potential targeting of METTL3 as cancer treatment, have not yet been highlighted. Here we summarize our current understanding both on the oncogenic and tumor-suppressive functions of METTL3, as well as the underlying molecular mechanisms. The well-documented protein structure of the METTL3/METTL14 heterodimer provides the basis for potential therapeutic targeting, which is also discussed in this review.