胃癌是消化系统最常见的恶性肿瘤之一,多数患者发现时已处于晚期,预后不佳.外科手术及化学治疗(化疗)仍是目前胃癌的主要治疗方式.N6-甲基腺嘌呤(N6-methyladenosine,m6A)是近年来肿瘤研究的热点.m6A作为真核生物中最常见的RNA修饰形式,可以调控RNA循环的各个阶段,包括RNA剪接、加工、降解和翻译等,从而调控RNA的表达和功能,在细胞分化、发育和代谢等各个环节中发挥关键作用.m6A去甲基化酶可去除RNA上的甲基基团,确保m6A甲基化是一个动态的可逆的过程.作为m6A甲基化过程的关键酶,m6A去甲基化酶——脂肪和肥胖相关蛋白(fat mass and obesity-associated protein,FTO)、AlkB同系物5(AlkB homolog 5,ALKBH5)、ALKBH3的失调能通过多种机制调控胃癌的演进过程,与胃癌的发生发展密切相关.m6A去甲基化酶通过调节信号通路,改变胃癌细胞的增殖和侵袭能力,影响胃癌对化疗药物的耐药性,参与调控胃癌的免疫应答及线粒体代谢,从而影响胃癌细胞的生长,有望成为一个全新的治疗靶点.该文综述了m6A去甲基化酶参与胃癌发生发展的分子机制,以及其表达和功能与胃癌生物学特性的关系,旨在为胃癌的早期诊断和靶向治疗提供新的研究思路.
Progress of research on m6A demethylases in gastric cancer
Gastric cancer(GC)is one of the most common malignancies in the digestive system.Many patients are found in advanced stage and have a poor prognosis.Surgery and chemotherapy remain the main treatments for gastric cancer.N6-methyladenosine(m6A)is a hot topic in tumor research in recent years.As the most common form of RNA modification in eukaryotes,m6A can regulate various stages of the RNA cycle,including RNA splicing,processing,degradation,and translation,thereby regulating RNA expression and function,playing a critical role in various pathways such as cell differentiation,development,and metabolism.The m6A demethylase can remove methyl groups on RNA,ensuring that m6A methylation is a dynamic and reversible process.As a key enzyme in the m6A methylation process,the imbalance of m6A demethylases fat mass and obesity-associated protein(FTO),AlkB homolog 5(ALKBH5)and ALKBH3 regulate the progression of gastric cancer through various mechanisms,which is closely related to the occurrence and development of gastric cancer.These m6A demethylases regulate the signaling pathway,alter the proliferation and invasion ability of gastric cancer cells,affect its resistance to chemotherapy drugs,participate in regulating the immune response and mitochondrial metabolism of gastric cancer,and affect the growth of gastric cancer cells.They are expected to become a novel therapeutic target.This article comprehensively summarizes the molecular mechanism of m6A demethylase involved in the occurrence and development of gastric cancer,and the relationship between its expression and function,and biological characteristics of m6A demethylase were reviewed,aiming to provide new research ideas for early diagnosis and targeted treatment of gastric cancer.
N6-methyladenosine(m6A)fat mass and obesity-associated protein(FTO)AlkB homolog 5(ALKBH5)ALKBH3gastric cancer
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