Zhang Zili, Xing Yu, Gao Wenqing, Yang Liping, Shi Junzhong, Song Weiliang, Li Tong
Department of Gastrointestinal Surgery, The Third Central Clinical College of Tianjin Medical University, Tianjin, China.
Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.
Bioengineered. 2022 May;13(5):11541-11550. doi: 10.1080/21655979.2022.2068920.
N-methyladenosine (mA) modification acts as the most prevalent internal modification in eukaryotic mRNA. Emerging evidence shows the critical biological roles of mA key enzymes in human cancers. However, the roles of mA binding protein IGF2BP2 in gastric cancer (GC) progression are still unclear. In this study, we confirmed that IGF2BP2 was highly expressed in GC cell lines and tumor tissues. Knocking down of IGF2BP2 suppressed cell proliferation and migration, and repressed xenograft tumor growth in vivo, while IGF2BP2 overexpression promoted the proliferation and migration. Mechanistically, we identified that IGF2BP2 regulated GC the proliferation/migration through recognizing the mA modification sites of SIRT1 mRNA. In general, our findings demonstrated a novel regulatory mechanism that IGF2BP2/SIRT1 axis modulated GC progression in an mA-dependent manner, suggesting that mA may be a therapeutic target for GC.
N6-甲基腺苷（m6A）修饰是真核生物信使核糖核酸（mRNA）中最普遍的内部修饰。新出现的证据表明m6A关键酶在人类癌症中具有重要的生物学作用。然而，m6A结合蛋白胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）在胃癌（GC）进展中的作用仍不清楚。在本研究中，我们证实IGF2BP2在GC细胞系和肿瘤组织中高表达。敲低IGF2BP2可抑制细胞增殖和迁移，并在体内抑制异种移植瘤生长，而IGF2BP2过表达则促进增殖和迁移。机制上，我们发现IGF2BP2通过识别沉默调节蛋白1（SIRT1）mRNA的m6A修饰位点来调节GC的增殖/迁移。总的来说，我们的研究结果证明了一种新的调控机制，即IGF2BP2/SIRT1轴以m6A依赖的方式调节GC进展，表明m6A可能是GC的一个治疗靶点。
