N<sup>6</sup>-methyladenosine regulates glycolysis of cancer cells through PDK4.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32444598.
- Also identified by DOI 10.1038/s41467-020-16306-5 and PMC identifier 7244544.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Studies on biological functions of N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification in mRNA have sprung up in recent years. We find m<sup>6</sup>A can positively regulate the glycolysis of cancer cells. Specifically, m<sup>6</sup>A-sequencing and functional studies confirm that pyruvate dehydrogenase kinase 4 (PDK4) is involved in m<sup>6</sup>A regulated glycolysis and ATP generation. The m<sup>6</sup>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<sup>6</sup>A by dm<sup>6</sup>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<sup>6</sup>A/PDK4 in tumor growth and progression of cervical and liver cancer. Our study reveals that m<sup>6</sup>A regulates glycolysis of cancer cells through PDK4.
Medical subject headings
- Adenosine
- Glycolysis
- Pyruvate Dehydrogenase Acetyl-Transferring Kinase
- Uterine Cervical Neoplasms