The crosstalk between RNA m6A epitranscriptome and TGFβ signaling pathway contributes to the arrest of cell cycle

被引：10
作者：
Li, Le [1 ,2 ]
Chen, Yong-Xian [1 ,2 ]
Yang, Bing [3 ]
Liao, Jian-You [3 ]
Peng, Jing-Wen [3 ]
Zhu, Shuang [1 ,2 ]
机构：
[1] Guangdong Pharmaceut Univ, Ctr Bioresources & Drug Discovery, Guangzhou 510006, Peoples R China
[2] Guangdong Pharmaceut Univ, Sch Biosci & Biopharmaceut, Guangdong Prov Key Lab Biotechnol Drug Candidates, Guangzhou 510006, Peoples R China
[3] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Med Res Ctr, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Peoples R China
来源：
GENE | 2020年 / 738卷
关键词：
N6-methyladenosine; WTAP; Epitranscriptome; TGE beta; Cell cycle; NUCLEAR-RNA; N6-METHYLADENOSINE; PROLIFERATION; METHYLATION; RECOGNITION; TRANSLATION;
D O I：
10.1016/j.gene.2020.144483
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
TGE beta signaling pathway is critical for the cell division, differentiation and apoptosis, the aberrant regulation of which will result in severe diseases including cancer. N6-methyl-adenosine (m(6)A) is one of the most abundant modifications on mRNA, it is unclear yet how m(6)A epitranscriptome response to stimulation of TGE beta. Here, we found that cellular m(6)A level of RNA was elevated after TGE beta treatment, which might be regulated by upregulation of WTAP and METTL3. MeRIP-Seq of mRNAs of MCF7 with or without treated by TGE beta showed that mRNA with upregulated m(6)A modification level after TGE beta treatment were enriched in TGE beta signaling pathway. Phosphorylated level of SMAD2 or SMAD3 induced by TGE beta was impaired when WTAP was silenced. Moreover, the m(6)A modification and mRNA level of JunB, which is known as a cell cycle inhibitor, both were increased after induction of TGE beta and decreased after knockdown of WTAP. Intriguingly, growth inhibition caused by TGE beta was rescued in WTAP-knockdown cells. Collectively, these results reveal the key role that m(6)A pathway playing in the cell cycle arrest induced by TGE beta signaling, providing new mechanisms explanation for growth inhibition mediated by TGE beta.
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页数：7
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