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

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, Qingjiao Li, Xuemei Fu () and Yang Xu ()
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Lili Yu: Sun Yat-sen University
Jinchul Kim: Sun Yat-sen University
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
Yang Xu: Sun Yat-sen University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-14437-3

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