N6-甲基腺苷(m6A)读码器 IGF2BP1 以 c-Myc 依赖的方式促进胃癌有氧糖酵解。
N-methyladenosine (mA) reader IGF2BP1 accelerates gastric cancer aerobic glycolysis in c-Myc-dependent manner.
机构信息
Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences, People's Hospital of Sichuan Provincial, Chengdu, Sichuan Province, 610101, China.
Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences, People's Hospital of Sichuan Provincial, Chengdu, Sichuan Province, 610101, China.
出版信息
Exp Cell Res. 2022 Aug 1;417(1):113176. doi: 10.1016/j.yexcr.2022.113176. Epub 2022 Apr 27.
The N-methyladenosine (mA) is involved in the regulation of cell proliferation and metastasis formation in multiple cancers. However, the biological significance of RNA mA reader IGF2BP1 and the modification of IGF2BP1 itself have not been fully investigated. Here, we analyzed the functions and mechanism of IGF2BP1 in gastric cancer (GC). Results showed that IGF2BP1 upregulated in GC tissue and acted as a predictor of poor prognosis for GC patients. Functionally, IGF2BP1 promoted the migration and aerobic glycolysis of GC cells in vitro. Moreover, IGF2BP1 knockdown repressed the tumor growth in vivo. We also demonstrated that IGF2BP1 directly interacted with c-MYC mRNA via m6A-dependent manner to by stabilize its stability. Overall, these findings demonstrated that mA reader IGF2BP1 facilitated the carcinogenic of GC in mA/c-Myc-dependent manner, which might provide critical therapeutic strategy for GC.
N6-甲基腺苷（m6A）参与多种癌症的细胞增殖和转移形成的调控。然而，RNA m6A 阅读蛋白 IGF2BP1 的生物学意义以及 IGF2BP1 自身的修饰尚未被充分研究。在这里，我们分析了 IGF2BP1 在胃癌（GC）中的功能和机制。结果表明，IGF2BP1 在 GC 组织中上调，并且可以作为 GC 患者预后不良的预测因子。在功能上，IGF2BP1 促进了 GC 细胞在体外的迁移和有氧糖酵解。此外，IGF2BP1 的敲低抑制了体内肿瘤的生长。我们还证明了 IGF2BP1 通过 m6A 依赖的方式直接与 c-MYC mRNA 相互作用，从而稳定其稳定性。总的来说，这些发现表明 m6A 阅读蛋白 IGF2BP1 通过 m6A/c-MYC 依赖性途径促进 GC 的致癌作用，这可能为 GC 提供了关键的治疗策略。
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