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N6-甲基腺嘌呤:胃癌中的机制、诊断价值、免疫治疗前景及挑战

The N6-methyladenosine:mechanisms, diagnostic value, immunotherapy prospec-ts and challenges in gastric cancer.

作者信息

Wu Wenzhang, Zhang Fan, Zhao Jun, He Puyi, Li Yumin

机构信息

Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, China.

Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, China; Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, 730000, China.

出版信息

Exp Cell Res. 2022 Jun 15;415(2):113115. doi: 10.1016/j.yexcr.2022.113115. Epub 2022 Mar 24.

Abstract

The N6-methyladenosine (mA) RNA modification is important in post-transcriptional regulation of RNA and are regulated reversibly by methyltransferases (writers), demethylases (erasers) and mA recognition proteins (readers). Changes in the structure and function of key RNAs contribute to the development of diseases, particularly tumors. Many abnormal expressions of molecules related to mA RNA methylation modification are discovered in gastric cancer (GC), which changes the methylation level and stability of target genes after transcription, and then regulates related metabolic pathways, affecting the occurrence and progression of GC. Therefore, an in-depth study of mA RNA modification in GC is conducive to the development of new tumor therapies and the achieve of individualized treatment. At present, both basic and clinical studies indicate that mA plays a complex and contentious role in GC. In this paper, we not only review the roles and mechanisms of mA modified related proteins, but also discuss the value of mA modulators in the clinical applications and current challenges of GC, aiming to provide research clues for the early diagnosis and explore the feasibility of mA related proteins as specific targets for GC immunotherapy.

摘要

N6-甲基腺嘌呤(m⁶A)RNA修饰在RNA的转录后调控中起着重要作用,并且受到甲基转移酶(写入器)、去甲基化酶(擦除器)和m⁶A识别蛋白(读取器)的可逆调控。关键RNA的结构和功能变化会导致疾病,特别是肿瘤的发生发展。在胃癌(GC)中发现了许多与m⁶A RNA甲基化修饰相关分子的异常表达,这改变了转录后靶基因的甲基化水平和稳定性,进而调节相关代谢途径,影响GC的发生和进展。因此,深入研究GC中的m⁶A RNA修饰有助于开发新的肿瘤治疗方法并实现个体化治疗。目前,基础研究和临床研究均表明m⁶A在GC中发挥着复杂且有争议的作用。在本文中,我们不仅综述了m⁶A修饰相关蛋白的作用和机制,还讨论了m⁶A调节剂在GC临床应用中的价值以及当前面临的挑战,旨在为早期诊断提供研究线索,并探索m⁶A相关蛋白作为GC免疫治疗特异性靶点的可行性。

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