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N6-methyladenosine regulates glycolysis of cancer cells through PDK4

Author

Listed:
  • Zihan Li

    (Sun Yat-sen University
    University of South China)

  • Yanxi Peng

    (Sun Yat-sen University
    Xiangnan University)

  • Jiexin Li

    (Sun Yat-sen University)

  • Zhuojia Chen

    (Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine)

  • Feng Chen

    (Sun Yat-sen University)

  • Jian Tu

    (University of South China)

  • Shuibin Lin

    (Sun Yat-sen University)

  • Hongsheng Wang

    (Sun Yat-sen University)

Abstract

Studies on biological functions of N6-methyladenosine (m6A) modification in mRNA have sprung up in recent years. We find m6A can positively regulate the glycolysis of cancer cells. Specifically, m6A-sequencing and functional studies confirm that pyruvate dehydrogenase kinase 4 (PDK4) is involved in m6A regulated glycolysis and ATP generation. The m6A 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 m6A by dm6ACRISPR 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 m6A/PDK4 in tumor growth and progression of cervical and liver cancer. Our study reveals that m6A regulates glycolysis of cancer cells through PDK4.

Suggested Citation

  • Zihan Li & Yanxi Peng & Jiexin Li & Zhuojia Chen & Feng Chen & Jian Tu & Shuibin Lin & Hongsheng Wang, 2020. "N6-methyladenosine regulates glycolysis of cancer cells through PDK4," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16306-5
    DOI: 10.1038/s41467-020-16306-5
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    Cited by:

    1. Wanzun Lin & Li Chen & Haojiong Zhang & Xianxin Qiu & Qingting Huang & Fangzhu Wan & Ziyu Le & Shikai Geng & Anlan Zhang & Sufang Qiu & Long Chen & Lin Kong & Jiade J. Lu, 2023. "Tumor-intrinsic YTHDF1 drives immune evasion and resistance to immune checkpoint inhibitors via promoting MHC-I degradation," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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