机构地区: 中山大学药学院
出 处: 《药学学报》 2019年第10期1771-1782,共12页
摘 要: N6-甲基腺苷(N6-methyladenosine, m^6A)修饰是真核生物信使RNA (messenger RNA, mRNA)中最常见的修饰之一,近年来已成为生命科学领域的研究热点。mRNA的m^6A修饰动态可逆,主要由甲基化酶(writers)、去甲基化酶(erasers)和识别蛋白(readers)所调控,从而参与RNA剪接、出入核、蛋白质翻译及降解等多种生物学过程。近年研究表明, m^6A在肿瘤发生发展中发挥重要作用。本文围绕m^6A的生物学功能,研究其在肿瘤细胞增殖、转移、能量代谢和血管生成等恶性生物学行为中的作用,阐述其在急性白血病、肝癌、结直肠癌等多种肿瘤中的作用及机制。目前,包括脂肪和肥胖相关蛋白和AlkB同源物5在内的m^6A相关酶的抑制剂正在开发中。本文进一步讨论了m^6A的潜在价值及其在癌症治疗中的相关靶点。 N6-methyladenosine(m^6A)modification is one of the most common modifications of eukaryotic mRNA,and has become a hotspot in the field of life sciences in recent years.m^6A modification is dynamically reversible in mammalian cells and regulated by m^6A methyltransferase(writers),demethylase(erasers),and'reader'proteins.m^6A can regulate various biological processes of mRNA such as RNA splicing,nuclear export,protein translation and degradation.Recent studies indicated that m^6A is important for the initiation and development of cancer.The present review summarized biological functions of m^6A on mRNA and discussed its roles in cell proliferation,migration,invasion,cell mentalism,and angiogenesis.Further,the m^6A can regulate the development of various cancers including acute myelocytic leukemia(AML),breast,liver and colorectal cancer.Nowadays,the inhibitors of m^6A related enzymes including fat-mass and obesity-associated protein and AlkB homolog 5 are being developed.We further discussed the potential values of m^6A and its related targets on cancer therapy and treatment.
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