N6-甲基腺苷(m6A)RNA修饰在生殖系统疾病中作用的研究进展

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (9): 1347-1351.

N6-甲基腺苷(m6A)RNA修饰在生殖系统疾病中作用的研究进展

张妍, 朱孟雯, 刘桐, 杨圣, 梁戈玉^*

东南大学公共卫生学院环境医学工程教育部重点实验室,江苏南京 210009

收稿日期:2020-07-30 修回日期:2020-11-17 出版日期:2021-09-05 发布日期:2021-09-02
通讯作者: *lianggeyu@163.com
基金资助:
国家自然科学基金(81972998)

Research progress on the role of N6-methyladenosine (m6A) RNA modification in reproductive system diseases

ZHANG Yan, ZHU Meng-wen, LIU Tong, YANG Sheng, LIANG Ge-yu^*

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China

Received:2020-07-30 Revised:2020-11-17 Online:2021-09-05 Published:2021-09-02
Contact: *lianggeyu@163.com

摘要/Abstract

摘要： N6-甲基腺苷(m6A)RNA修饰是发生在RNA腺嘌呤第6位N原子上的一种转录后的甲基化修饰,调控mRNA的结构、稳定性、剪接、输出、转译和衰变等,进而广泛影响各种生物的生命过程。本文总结了在生殖系统疾病及乳腺癌发生发展过程中各种m6A甲基化酶的作用及机制,旨在为生殖系统疾病及乳腺癌早期诊断、治疗及预后判断提供新的依据。

关键词: N6-甲基腺苷(m6A), 生殖系统疾病, 表观遗传, 乳腺癌

Abstract: N6-methyladenosine (m6A) RNA modification is a post-transcriptional modification occurring on the 6th N atom of RNA adenine (A), regulating the structure, stability, splicing, output, translation and decay of mRNA, and thus extensively affecting the life processes of various organisms.This paper summarized the role and mechanism of various m6A methylase in the occurrence and development of reproductive system diseases and breast caner, in order to provide new basis for early diagnosis, treatment and improved prognosis of reproductive system diseases and breast caner.

Key words: N6-methyladenosine(m6A), reproductive system diseases, epigenetics, breast cancer

中图分类号:

R394.3

张妍, 朱孟雯, 刘桐, 杨圣, 梁戈玉. N6-甲基腺苷(m6A)RNA修饰在生殖系统疾病中作用的研究进展[J]. 基础医学与临床, 2021, 41(9): 1347-1351.

ZHANG Yan, ZHU Meng-wen, LIU Tong, YANG Sheng, LIANG Ge-yu. Research progress on the role of N6-methyladenosine (m6A) RNA modification in reproductive system diseases[J]. Basic & Clinical Medicine, 2021, 41(9): 1347-1351.

参考文献

[1]Liu T, Wei Q, Jin J, et al. The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation[J]. Nucleic Acids Res, 2020,48:3816-3831.
[2]Zhu H, Gan X, Jiang X, et al. ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and Bcl-2[J]. J Exp Clin Cancer Res, 2019,38:163.doi: 10.1186/s13046-019-1159-2.
[3]Ding C, Zou Q, Ding J, et al. Increased N6-methyladenosine causes infertility is associated with FTO expression[J]. J Cell Physiol, 2018,233:7055-7066.
[4]Huang B, Ding C, Zou Q, et al. Cyclophosphamide regulates N6-methyladenosine and m6A RNA enzyme levels in human granulosa cells and in ovaries of a premature ovarian aging mouse model[J]. Front Endocrinol (Lausanne), 2019,10:415.doi: 10.3389/fendo.2019.00415.
[5]Fan Y, Zhang C, Zhu G. Profiling of RNA N6-methyladenosine methylation during follicle selection in chicken ovary[J]. Poult Sci, 2019,98:6117-6124.
[6]Liu L, Liu X, Dong Z, et al. N6-methyladenosine-related genomic targets are altered in breast cancer tissue and associated with poor survival[J]. J Cancer, 2019,10:5447-5459.
[7]Wu L, Wu D, Ning J, et al. Changes of N6-methyladenosine modulators promote breast cancer progression[J]. BMC Cancer, 2019,19:326.doi: 10.1186/s12885-019-5538-z.
[8]Niu Y, Lin Z, Wan A, et al. RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3[J]. Mol Cancer, 2019,18:46.doi: 10.1186/s12943-019-1004-4.
[9]Wang H, Xu B, Shi J. N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2[J]. Gene, 2020,722:144076. doi: 10.1016/j.gene.2019.144076.
[10]Fry NJ, Law BA, Ilkayeva OR, et al. N(6)-methyladenosine contributes to cellular phenotype in a genetically-defined model of breast cancer progression[J]. Oncotarget, 2018,9:31231-31243.
[11]Wang X, Li Z, Kong B, et al. Reduced m(6)A mRNA methylation is correlated with the progression of human cervical cancer[J]. Oncotarget, 2017,8:98918-98930.
[12]Zou D, Dong L, Li C, et al. The m(6)A eraser FTO facilitates proliferation and migration of human cervical cancer cells[J]. Cancer Cell Int, 2019,19:321.doi: 10.1186/s12935-019-1045-1.
[13]Zhou S, Bai ZL, Xia D, et al. FTO regulates the chemo-radiotherapy resistance of cervical squamous cell carcino-ma (CSCC) by targeting beta-catenin through mRNA demethylation[J]. Mol Carcinog, 2018,57:590-597.
[14]Liu J, Eckert MA, Harada BT, et al. m(6)A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer[J]. Nat Cell Biol, 2018,20:1074-1083.
[15]Li XC, Jin F, Wang BY, et al. The m6A demethylase ALKBH5 controls trophoblast invasion at the maternal-fetal interface by regulating the stability of CYR61 mRNA[J]. Theranostics, 2019,9:3853-3865.
[16]Ivanova I, Much C, Di Giacomo M, et al. The RNA m(6)A reader YTHDF2 is essential for the post-transcriptional regulation of the maternal transcriptome and oocyte competence[J]. Molecular cell, 2017,67:1059-1067.
[17]Sui X, Hu Y, Ren C, et al. METTL3-mediated m(6)A is required for murine oocyte maturation and maternal-to-zygotic transition[J]. Cell Cycle, 2020,19:1-14.
[18]Cai J, Yang F, Zhan H, et al. RNA m(6)A methyltransferase METTL3 promotes the growth of prostate cancer by regulating Hedgehog pathway[J]. Onco Targets Ther, 2019,12:9143-9152.
[19]Lobo J, Costa AL, Cantante M, et al. m(6)A RNA modification and its writer/reader VIRMA/YTHDF3 in testicular germ cell tumors: a role in seminoma phenotype maintenance[J]. J Transl Med, 2019,17:79.doi: 10.1186/s12967-019-1837-z.
[20]Chen Y, Wang J, Xu D, et al. m(6)A mRNA methylation regulates testosterone synthesis through modulating autophagy in Leydig cells[J]. Autophagy, 2021,17:457-475.
[21]Zhao TX, Wang JK, Shen LJ, et al. Increased m6A RNA modification is related to the inhibition of the Nrf2-mediated antioxidant response in di-(2-ethylhexyl) phthalate-induced prepubertal testicular injury[J]. Environ Pollut, 2020,259:113911.doi: 10.1016/j.envpol.2020.113911.
[22]Yuan JT, Gatti DM, Philip VM, et al. Genome-wide association for testis weight in the diversity outbred mouse population[J]. Mamm Genome, 2018,29:310-324.
[23]Huang T, Liu Z, Zheng Y, et al. YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via m(6)A/mRNA pathway[J]. Cell Death Dis, 2020,11:37.doi: 10.1038/s41419-020-2235-4.
[24]Tang C, Klukovich R, Peng H, et al. ALKBH5-depen-dent m6A demethylation controls splicing and stability of long 3′-UTR mRNAs in male germ cells[J]. Proc Natl Acad Sci U S A, 2018,115:325-333.
[25]Yang Y, Huang W, Huang J T, et al. Increased N6-methyladenosine in human sperm RNA as a risk factor for asthenozoospermia[J]. Sci Rep, 2016,6:24345.doi: 10.1038/srep24345.