FTO regulates myoblast proliferation by controlling CCND1 expression in an m6A-YTHDF2-dependent manner

被引：27

作者：

Deng, Kaiping ^{[1
]}

Zhang, Zhen ^{[1
]}

Ren, Caifang ^{[2
]}

Liang, Yaxu ^{[1
]}

Gao, Xiaoxiao ^{[1
]}

Fan, Yixuan ^{[1
]}

Wang, Feng ^{[1
]}

机构：

[1] Nanjing Agr Univ, Inst Sheep & Goat Sci, Nanjing 210095, Peoples R China

[2] Jiangsu Univ, Sch Med, Dept Pathol, Zhenjiang 212000, Jiangsu, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2021年 / 401卷 / 02期

基金：

国家重点研发计划;

关键词：

m(6)A modification; FTO; Cell cycle; Cell proliferation; Myoblast; CELL-CYCLE PROGRESSION; RNA METHYLATION; NUCLEAR-RNA; STEM-CELLS; GENE; DEMETHYLASE; PROTEIN; FATE;

D O I：

10.1016/j.yexcr.2021.112524

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

N6-Methyladenosine (m(6)A) modification is the most abundant chemical modification in mRNA, and it participates in various biological processes, such as cell differentiation and proliferation. However, little is known about the function of m(6)A demethylase fat mass and obesity-associated (FTO) in myoblast proliferation. Here, we demonstrated that knockdown of FTO can significantly inhibit myoblast proliferation and promote apoptosis. RNA sequencing analysis revealed that a lot of downregulated genes in FTO knockdown cells are associated with cell cycle and apoptosis. Furthermore, silencing FTO drastically decreased cyclin D1 (CCND1) expression through YTHDF2-mediated mRNA degradation, thereby delaying the progression of G1 phase, and leading to impaired myoblast proliferation. These findings unraveled that FTO regulates myoblast proliferation by controlling CCND1 expression in an m(6)A-YTHDF2-dependent manner, which highlights the critical roles of m(6)A modification in myoblast proliferation.

引用

页数：10

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