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MTR4 drives liver tumorigenesis by promoting cancer metabolic switch through alternative splicing

Author

Listed:
  • Lili Yu

    (Sun Yat-sen University
    Southern Medical University)

  • Jinchul Kim

    (Sun Yat-sen University
    University of California, San Diego)

  • Lei Jiang

    (Southern Medical University)

  • Bingbing Feng

    (Southern Medical University)

  • Yue Ying

    (Southern Medical University)

  • Kai-yuan Ji

    (Sun Yat-sen University)

  • Qingshuang Tang

    (Southern Medical University)

  • Wancheng Chen

    (Southern Medical University)

  • Taoyi Mai

    (Sun Yat-sen University)

  • Wenlong Dou

    (Southern Medical University)

  • Jianlong Zhou

    (Southern Medical University)

  • Le-yang Xiang

    (Southern Medical University)

  • Yang-fan He

    (Sun Yat-sen University Cancer Center)

  • Dinghua Yang

    (Southern Medical University)

  • Qingjiao Li

    (Sun Yat-sen University)

  • Xuemei Fu

    (Sun Yat-sen University
    Shenzhen Children’s Hospital)

  • Yang Xu

    (Sun Yat-sen University
    Southern Medical University
    University of California, San Diego)

Abstract

The metabolic switch from oxidative phosphorylation to glycolysis is required for tumorigenesis in order to provide cancer cells with energy and substrates of biosynthesis. Therefore, it is important to elucidate mechanisms controlling the cancer metabolic switch. MTR4 is a RNA helicase associated with a nuclear exosome that plays key roles in RNA processing and surveillance. We demonstrate that MTR4 is frequently overexpressed in hepatocellular carcinoma (HCC) and is an independent diagnostic marker predicting the poor prognosis of HCC patients. MTR4 drives cancer metabolism by ensuring correct alternative splicing of pre-mRNAs of critical glycolytic genes such as GLUT1 and PKM2. c-Myc binds to the promoter of the MTR4 gene and is important for MTR4 expression in HCC cells, indicating that MTR4 is a mediator of the functions of c-Myc in cancer metabolism. These findings reveal important roles of MTR4 in the cancer metabolic switch and present MTR4 as a promising therapeutic target for treating HCC.

Suggested Citation

  • Lili Yu & Jinchul Kim & Lei Jiang & Bingbing Feng & Yue Ying & Kai-yuan Ji & Qingshuang Tang & Wancheng Chen & Taoyi Mai & Wenlong Dou & Jianlong Zhou & Le-yang Xiang & Yang-fan He & Dinghua Yang & Qi, 2020. "MTR4 drives liver tumorigenesis by promoting cancer metabolic switch through alternative splicing," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14437-3
    DOI: 10.1038/s41467-020-14437-3
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