miR372 Promotes Progression of Liver Cancer Cells by Upregulating erbB-2 through Enhancement of YB-1

Zhuojia Lin; Yanan Lu; Qiuyu Meng; Chen Wang; Xiaonan Li; Yuxin Yang; Xiaoru Xin; Qidi Zheng; Jie Xu; Xin Gui; Tianming Li; Hu Pu; Wujun Xiong; Jiao Li; Song Jia; Dongdong Lu

doi:10.1016/j.omtn.2018.04.001

Molecular Therapy: Nucleic Acids (Jun 2018)

miR372 Promotes Progression of Liver Cancer Cells by Upregulating erbB-2 through Enhancement of YB-1

Zhuojia Lin,
Yanan Lu,
Qiuyu Meng,
Chen Wang,
Xiaonan Li,
Yuxin Yang,
Xiaoru Xin,
Qidi Zheng,
Jie Xu,
Xin Gui,
Tianming Li,
Hu Pu,
Wujun Xiong,
Jiao Li,
Song Jia,
Dongdong Lu

Affiliations

Zhuojia Lin: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Yanan Lu: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Qiuyu Meng: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Chen Wang: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Xiaonan Li: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Yuxin Yang: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Xiaoru Xin: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Qidi Zheng: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Jie Xu: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Xin Gui: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Tianming Li: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Hu Pu: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Wujun Xiong: Department of Hepatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Jiao Li: School of Medicine, Tongji University, Shanghai 200092, China
Song Jia: School of Medicine, Tongji University, Shanghai 200092, China
Dongdong Lu: Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China

DOI: https://doi.org/10.1016/j.omtn.2018.04.001
Journal volume & issue: Vol. 11, no. C
pp. 494 – 507

Abstract

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MicroRNAs are known to be involved in carcinogenesis. Recently, microRNA-372 (miR372) has been proven to play a substantial role in several human cancers, but its functions in liver cancer remain unclear. Herein, our results demonstrate that miR372 accelerates growth of liver cancer cells in vitro and in vivo. Mechanistically, miR372 enhances expression of Y-box-binding protein 1 (YB-1) by targeting for phosphatase and tensin homolog (PTEN) directly and consequently promotes phosphorylation of YB-1 via HULC looping dependent on ERK1/2 and PTEN. In particular, HULC knockdown or PTEN overexpression abrogated this miR372 action. Moreover, miR372 inhibits the degradation of β-catenin dependent on phosphorylation of YB-1 and then enhances the expression and activity of pyruvate kinase M2 isoform (PKM2) by β-catenin-LEF/TCF4 pathway. Furthermore, the loading of LEF/TCF4 on PKM2 promoter region was significantly increased in miR372 overexpressing Hep3B, and thus, glycolytic proton efflux rate (glycoPER) was significantly increased in rLV-miR372 group compared to the rLV group. Moreover, β-catenin knockdown abrogates this function of miR372. Ultimately, miR372 promotes the expression of erbB-2 through PKM2-pH3T11-acetylation on histone H3 lysine 9 (H3K9Ac) pathway. Of significance, both YB-1 knockdown and erbB-2 knockdown abrogate oncogenic action of miR372. Our observations suggest that miR372 promotes liver cancer cell cycle progress by activating cyclin-dependent kinase 2 (CDK2)-cyclin E-P21/Cip1 complex through miR372-YB-1-β-catenin-LEF/TCF4-PKM2-erbB-2 axis. This study elucidates a novel mechanism for miR372 in liver cancer cells and suggests that miR372 can be used as a novel therapeutic target of liver cancer.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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