m^6 A RNA甲基化修饰异常在肿瘤中的作用

The Role of m^6A RNA Methylated Abnormality in Tumor

N6-甲基腺嘌呤(N6-methyladenosine,m6A)是真核生物信使RNA(messenger RNA,mRNA)含量最多的化学修饰之一。m6A修饰主要由m6A甲基转移酶(methyltransferase)催化,m6A去甲基酶(demethylase)去除,并由m6A结合蛋白(binding protein)识别。它广泛参与调控mRNA剪接、加工、翻译和降解等生命周期的各个阶段,且与肥胖和肿瘤等多种疾病及异常的生理功能相关。近年的研究发现,肿瘤中m6A相关蛋白质(METTL3/14、WTAP、FTO、ALKBH5、YTHDFs)的异常表达,引发m6A甲基化的失调,调控致癌基因和抑癌基因的表达参与肿瘤的发生与发展,并与患者预后不良密切相关。随着RNA免疫沉淀测序技术与高通量测序技术和液相色谱等检测技术的快速发展,有关m6A在肿瘤发生发展中的作用机制研究的进展迅猛,靶向m6A也成为肿瘤临床治疗的新方向。本文重点对m6A RNA甲基化相关因子在癌症发生发展中的作用及机制进行综述,总结m6A RNA甲基化检测技术的最新进展,梳理现有文献报道的脱甲基酶抑制剂大黄酸、甲氯芬那酸2(meclofenamic acid2,MA2)和右旋羟戊二酸(R-2-hydroxyglutarate,R-2HG)等在肿瘤靶向治疗中的运用,为以m6A RNA甲基化为切入点的肿瘤防治研究提供思路与理论参考。

N6-methyladenosine(m6A),one of the most chemical modifications,is highly detected in eukaryotic messenger RNA(mRNA).m6A modification is mainly catalyzed by m6A methyltransferase,removed by m6A demethylase,and recognized by m6A binding protein.m6A RNA modification is widely involved in the regulation of mRNA splicing,processing,translation and degradation in all stages of the life cycle.It is related to obesity,tumor,and other diseases.Recently,it has been found that abnormal expression of m6A-related proteins(METTL3/14,WTAP,FTO,ALKBH5,YTHDFs)in tumors can lead to the imbalance of m6A methylation.The oncogenes and tumor suppressors are involved in the occurrence and development of tumors,and are closely related to the prognosis of patients.With the rapid development of RNA immunoprecipitation sequencing technology,high-throughput sequencing technology,liquid chromatography and other detection technologies,the role of m6A in the occurrence and development of tumors has been further uncovered,and targeting m6A has become a new direction of tumor treatment.This paper focuses on the role and mechanism of m6A RNA methylation related factors in the development of cancer and summarized the latest development of m6A RNA methylation detection technology,including the application of demethylase inhibitors such as Rhein,meclofenamic acid2(MA2),and R-2-hydroxyglutarate(R-2HG).This paper also reviewed the existing literature in tumor targeting therapy and provided summary in tumor prevention and potential treatment with m6A RNA methylation.