Research Paper Volume 11, Issue 18 pp 7639—7662

miR-125a-5p inhibits tumorigenesis in hepatocellular carcinoma

Xin Xu 1, , Yuquan Tao 1, , Yongjie Niu 1, , Zhixian Wang 1, , Congcong Zhang 1, , Yongchun Yu 1, 2, , Lifang Ma 2, 3, ,

  • 1 Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, P.R. China
  • 2 Institute for Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China
  • 3 Department of Clinical Laboratory Medicine, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, P.R. China

received: June 14, 2019 ; accepted: September 7, 2019 ; published: September 17, 2019 ;

https://doi.org/10.18632/aging.102276
How to Cite

Copyright © 2019 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers world-wide. miR-125a-5p is a tumor suppressor in HCC and other cancers, but its mechanisms of action during HCC tumorigenesis remain largely unknown. In this study, we found that miR-125a-5p expression was significantly lower in HCC tissues and cell lines than matched normal tissues and liver cells. miR-125a-5p overexpression inhibited HCC cell proliferation and induced apoptosis in vitro and in vivo, while miR-125a-5p knockdown had the opposite effects. In addition, PTPN1 and MAP3K11 were identified as targets of miR-125a-5p. Knocking down PTPN1 and MAP3K11 activated the JNK MAPK signaling pathway to suppress HCC cell proliferation and induce apoptosis. Our findings suggest that miR-125a-5p may be a useful therapeutic target for treatment of HCC patients.

Abbreviations

HCC: Hepatocellular carcinoma; miRNAs: microRNAs; UTR: untranslated region; PTPN1: protein tyrosine phosphatase N1; PTP1B: protein tyrosine phosphatase 1B; MAP3K11: mitogen activated protein kinase kinasekinase 11; MLK3: mixed lineage kinase 3; JNK: c-Jun-N-terminal kinase; MAPK: mitogen-activated protein kinase; MAP2Ks: mitogen activated protein kinase kinases.