N6-甲基腺嘌呤甲基转移酶METTL3在泌尿系统肿瘤中的研究进展

The research progress of N6-methyladenosine methyltransferase METTL3 in urologic tumors

N6-甲基腺嘌呤(N6-methyladenosine,m^(6)A)是真核生物RNA分子中广泛存在的一种化学修饰。m^(6)A修饰由甲基转移酶和去甲基化酶共同催化调节,通过甲基化阅读蛋白的识别,影响mRNA剪接、加工、翻译和降解。甲基转移酶3(methyltransferase-like 3,METTL3)是m^(6)A甲基转移酶复合物的催化核心因子,其在泌尿系统肿瘤中的异常表达导致m^(6)A修饰水平改变,调控下游诸多编码和非编码基因,进而影响肿瘤的增殖、侵袭、转移和耐药性。随着METTL3在肿瘤中的作用被不断深入挖掘,其抑制剂的探索也成为了研究热点。因此,本文就METTL3在不同阅读蛋白的协同下,作用于不同靶标分子和下游信号通路,从而参与泌尿系统肿瘤发生和发展的机制进行综述,同时对METTL3抑制剂的研究进展进行总结,以期为肿瘤的预防、诊断和治疗提供新的研究思路和参考。

N6-methyladenosine(m^(6)A)represents one of the most abundant modifications in eukaryotes RNA.M6A modification is catalyzed and modified by m^(6)A methyltransferases and demethylases.The fates of m^(6)A-modified mRNAs rely on the functions of distinct“reader”proteins that recognize them,which may affect the splicing,processing,translation or degradation of the target mRNAs.Methyltransferase-like 3(METTL3)is a catalytic core component of m^(6)A methyltransferase compound,whose abnormal expression could lead to disordered m^(6)A modifications and further influence the proliferation,invasion,migration and drug resistance of tumor cells.As the functions of METTL3 have been explored in depth,METTL3 inhibitors have become research hotspots.Therefore,this review focus on the different target molecules and downstream signaling pathways affected by METTL3 with the assistance of different readers in the tumorigenesis and progression of urologic tumors,and summarizes the research progress of METTL3 inhibitors,in the hope to provide insights for the prevention,diagnosis and treatment of tumors.