METTL3介导的ADAMTS9抑制促进胃癌血管生成和癌变

Wang Nuofan, Huo Xinying, Zhang Baoguo, Chen Xiaoxiang, Zhao Shuli, Shi Xuesong, Xu Hao, Wei Xiaowei

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Front Oncol. 2022 Apr 28;12:861807. doi: 10.3389/fonc.2022.861807. eCollection 2022.

The role of methyltransferase-like 3 (METTL3), which participates in catalyzing N-methyladenosine (m6A) RNA modification, in gastric cancer (GC) is unclear. Here, we found that METTL3 was overexpressed in human GC. Functionally, we verified that METTL3 promoted tumor cell proliferation and angiogenesis through a series of phenotypic experiments. Subsequently, ADAMTS9 was identified as the downstream effector of METTL3 in GC, which could be degraded by the YTHDF2-dependent pathway. Finally, the data suggested that METTL3 might facilitate GC progression through the ADAMTS9-mediated PI3K/AKT pathway. Our study unveiled the fundamental mechanisms of METTL3 in GC progression. The clinical value of METTL3 in GC deserves further exploration.

参与催化N-甲基腺苷（m6A）RNA修饰的类甲基转移酶3（METTL3）在胃癌（GC）中的作用尚不清楚。在此，我们发现METTL3在人类胃癌中过表达。在功能上，我们通过一系列表型实验证实METTL3促进肿瘤细胞增殖和血管生成。随后，ADAMTS9被鉴定为GC中METTL3的下游效应因子，其可通过YTHDF2依赖途径被降解。最后，数据表明METTL3可能通过ADAMTS9介导的PI3K/AKT途径促进GC进展。我们的研究揭示了METTL3在GC进展中的基本机制。METTL3在GC中的临床价值值得进一步探索。