N 6 -methyladenosine regulates glycolysis of cancer cells through PDK4
NATURE COMMUNICATIONS(2020)
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 5′UTR 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.
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关键词
Cancer metabolism,Oncology,Science,Humanities and Social Sciences,multidisciplinary
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