N6-甲基腺苷在肝细胞癌发生发展中的作用

马可; 赵礼金

doi:10.3969/j.issn.1001-5256.2021.09.042

N6-甲基腺苷在肝细胞癌发生发展中的作用

DOI: 10.3969/j.issn.1001-5256.2021.09.042

马可,
赵礼金^,

遵义医科大学附属医院肝胆胰外科，贵州遵义 563000

基金项目:

国家自然科学基金 (81960125);

贵州省教育厅创新群体重大研究项目 (Qian Jiao He KY Zi〔2016〕039)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：马可负责课题设计，资料分析，撰写论文；赵礼金负责拟定写作思路，指导文章的撰写并最后定稿。

详细信息

通信作者:
赵礼金，zhaolijin66@sina.com

中图分类号: R735.7
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- 被引次数: 0
出版历程
- 收稿日期: 2021-02-01
- 录用日期: 2021-03-18
- 出版日期: 2021-09-20

Role of N6-methyladenosine in the development and progression of hepatocellular carcinoma

Ke MA,
Lijin ZHAO^,

Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China

Research funding:

National Natural Science Foundation of China (81960125);

Major Research Projects of Innovative Groups of Guizhou Provincial Department of Education (Qian Jiao He KY Zi〔2016〕039)

摘要

摘要: 肝细胞癌是原发性肝癌中最为常见的一种类型，具有较高的发病率和死亡率。N6-甲基腺苷(m6A)的异常修饰将会促进肝细胞癌的发生与发展。叙述了m6A的结构与功能并总结了决定m6A功能的甲基化酶复合物，包括甲基转移酶(编辑器)、去甲基酶(消码器)和m6A结合蛋白(读码器)在肝细胞癌中的作用机制。认为需要更深入的研究阐明甲基化酶复合物在肝细胞癌中作用的多样性和特异性，以期使之成为预防和治疗肝细胞癌的新靶点。
- 癌，肝细胞 /
- N6-甲基腺苷 /
- 甲基转移酶类 /
- 去甲基酶 /
- m6A结合蛋白
Abstract: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has relatively high incidence and mortality rates. Abnormal modification of N6-methyladenosine (m6A) may promote the development and progression of HCC. This article describes the structure and function of m6A and summarizes the mechanism of action of methylase complexes which decide the function of m6A in HCC, including methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers). It is pointed out that more in-depth studies are needed to clarify the diverse and specific role of methylase complexes in HCC, so as to help them become the new targets for the prevention and treatment of HCC in the future.
- Carcinoma, Hepatocellular /
- N6-Methyladenosine /
- Methyltransferases /
- Demethylase /
- m6A Binding Proteins

HTML全文

表 1 m6A调节因子在HCC中的作用及机制

调节因子	作用	机制	参考文献
METTL3	促进HCC发生与发展	抑制SOCS2的表达促进HCC细胞的增殖和迁移	[21]
		增加LINC00958的表达抑制miR-3619-5p，导致HDGF表达上调，促进HCC中的脂肪形成	[23]
		与DGCR8结合，通过上调miR-873-5p抑制SMG1的表达	[24]
	抑制HCC发展和转移	UBC9诱导METTL3泛素化使其活性降低，导致snail mRNA的稳定性增加	[22]
	增加HCC对索拉非尼的敏感性	上调FOXO3抑制自噬的发生	[25]
WTAP	促进HCC发展	抑制ETS1与HUR结合导致ETS1降解，促进HCC细胞增殖	[27]
KIAA1429	促进HCC发展	抑制GATA3的表达促进HCC的增殖和转移	[28]
		抑制ID2的表达促进HCC的迁移和侵袭	[29]
METTL14	抑制HCC发展	通过DGCR8促进pri-miRNA-126成熟，抑制HCC的转移	[30]
ALKBH5	抑制HCC发生与发展	下调LYPD1的表达抑制HCC细胞的增殖和侵袭	[37]
FTO	促进HCC发展	通过增加PKM2的表达促进HCC细胞增殖	[35]
	抑制HCC发展	下调CUL4A的表达抑制HCC的细胞增殖	[38]
		FTO降低导致GNAO1表达下降	[39]
YTHDF1	促进HCC发展	激活FZD5/WNT/β-catenin信号通路促进HCC细胞的增殖、迁移和侵袭	[19]
		促进snail的表达，诱导上皮-间充质转化的发生	[41]
YTHDF2	促进HCC肺转移	促进OCT4的表达，进而增加HCC干细胞表型，促进HCC肺转移	[42]
	抑制HCC发展	抑制HCC的炎症、血管重建和转移	[44]
		下调EGFR的表达抑制HCC细胞的增殖	[45]

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