N6-methyladenosine regulates glycolysis of cancer cells through PDK4

被引：246

作者：

Li, Zihan ^{[1
,2
]}

Peng, Yanxi ^{[1
,3
]}

Li, Jiexin ^{[1
]}

Chen, Zhuojia ^{[4
]}

Chen, Feng ^{[1
]}

Tu, Jian ^{[2
]}

Lin, Shuibin ^{[5
]}

Wang, Hongsheng ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangdong Key Lab Chiral Mol & Drug Discovery, Guangzhou 510006, Guangdong, Peoples R China

[2] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China

[3] Xiangnan Univ, Dept Basic Med, Chenzhou 423000, Hunan, Peoples R China

[4] Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Peoples R China

[5] Sun Yat Sen Univ, Affiliated Hosp 1, Ctr Translat Med, Guangzhou, Peoples R China

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

METHYLTRANSFERASE METTL3 PROMOTES; MESSENGER-RNA METHYLATION; STEM-LIKE CELLS; TRANSCRIPTION FACTORS; BREAST-CANCER; NUCLEAR-RNA; DEMETHYLASE; METABOLISM; EXPRESSION; TRANSLATION;

D O I：

10.1038/s41467-020-16306-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Studies on biological functions of N-6-methyladenosine (m(6)A) modification in mRNA have sprung up in recent years. We find m(6)A can positively regulate the glycolysis of cancer cells. Specifically, m(6)A-sequencing and functional studies confirm that pyruvate dehydrogenase kinase 4 (PDK4) is involved in m(6)A regulated glycolysis and ATP generation. The m(6)A modified 5UTR of PDK4 positively regulates its translation elongation and mRNA stability via binding with YTHDF1/eEF-2 complex and IGF2BP3, respectively. Targeted specific demethylation of PDK4 m(6)A by dm(6)ACRISPR system can significantly decrease the expression of PDK4 and glycolysis of cancer cells. Further, TATA-binding protein (TBP) can transcriptionally increase the expression of Mettl3 in cervical cancer cells via binding to its promoter. In vivo and clinical data confirm the positive roles of m(6)A/PDK4 in tumor growth and progression of cervical and liver cancer. Our study reveals that m(6)A regulates glycolysis of cancer cells through PDK4. p id=Par ysregulation of N6-Methyladenosine (m(6)A) is associated with cancer progression. Here, authors show that m(6)A methylation of pyruvate dehydrogenase kinase 4 (PDK4) positively regulates its mRNA stability and translation, and consequently affects glycolysis in cancer cells

引用

页数：16

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