N(6)-methyladenosine regulates glycolysis of cancer cells through PDK4

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 invo...

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Autores principales: Li, Zihan, Peng, Yanxi, Li, Jiexin, Chen, Zhuojia, Chen, Feng, Tu, Jian, Lin, Shuibin, Wang, Hongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244544/
https://www.ncbi.nlm.nih.gov/pubmed/32444598
http://dx.doi.org/10.1038/s41467-020-16306-5
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author Li, Zihan
Peng, Yanxi
Li, Jiexin
Chen, Zhuojia
Chen, Feng
Tu, Jian
Lin, Shuibin
Wang, Hongsheng
author_facet Li, Zihan
Peng, Yanxi
Li, Jiexin
Chen, Zhuojia
Chen, Feng
Tu, Jian
Lin, Shuibin
Wang, Hongsheng
author_sort Li, Zihan
collection PubMed
description 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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spelling pubmed-72445442020-06-03 N(6)-methyladenosine regulates glycolysis of cancer cells through PDK4 Li, Zihan Peng, Yanxi Li, Jiexin Chen, Zhuojia Chen, Feng Tu, Jian Lin, Shuibin Wang, Hongsheng Nat Commun Article 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. Nature Publishing Group UK 2020-05-22 /pmc/articles/PMC7244544/ /pubmed/32444598 http://dx.doi.org/10.1038/s41467-020-16306-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Li, Zihan
Peng, Yanxi
Li, Jiexin
Chen, Zhuojia
Chen, Feng
Tu, Jian
Lin, Shuibin
Wang, Hongsheng
N(6)-methyladenosine regulates glycolysis of cancer cells through PDK4
title N(6)-methyladenosine regulates glycolysis of cancer cells through PDK4
title_full N(6)-methyladenosine regulates glycolysis of cancer cells through PDK4
title_fullStr N(6)-methyladenosine regulates glycolysis of cancer cells through PDK4
title_full_unstemmed N(6)-methyladenosine regulates glycolysis of cancer cells through PDK4
title_short N(6)-methyladenosine regulates glycolysis of cancer cells through PDK4
title_sort n(6)-methyladenosine regulates glycolysis of cancer cells through pdk4
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244544/
https://www.ncbi.nlm.nih.gov/pubmed/32444598
http://dx.doi.org/10.1038/s41467-020-16306-5
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