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Research Paper|Volume 13, Issue 8|pp 12046—12057

Hsa-miR-107 regulates chemosensitivity and inhibits tumor growth in hepatocellular carcinoma cells

Hsin-An Chen1,2,3,4, Chi-Cheng Li5, Yu-Jung Lin6, Tso-Fu Wang7, Ming-Cheng Chen8, Yen-Hao Su1,2,3,4, Yu-Lan Yeh9,10, V. Vijaya Padma11, Po-Hsiang Liao3, Chih-Yang Huang6,12,13,14,15
  • 1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei City 250, Taiwan
  • 2Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 250, Taiwan
  • 3Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan
  • 4TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei City 250, Taiwan
  • 5Center of Stem Cell & Precision Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
  • 6Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
  • 7Department of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
  • 8Division of Colorectal Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung 407, Taiwan
  • 9Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan
  • 10Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 356, Taiwan
  • 11Department of Biotechnology, Bharathiar University, Coimbatore 641046, India
  • 12Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 970, Taiwan
  • 13Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan
  • 14Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan
  • 15Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 413, Taiwan
Received: January 21, 2021Accepted: March 25, 2021Published: April 26, 2021
https://doi.org/10.18632/aging.202908

Copyright: © 2021 Chen 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 is a common type of liver cancer. Resistance to chemotherapeutic agents is a major problem in cancer therapy. MicroRNAs have been reported in cancer development and tumor growth; however, the relationship between chemoresistance and hepatocellular carcinoma needs to be fully investigated. Here, we treated hepatocellular carcinoma cell line (HA22T) with a histone deacetylase inhibitor to establish hepatocellular carcinoma-resistant cells (HDACi-R) and investigated the molecular mechanisms of chemoresistance in HCC cells. Although histone deacetylase inhibitor could not enhance cell death in HDACi-R but upregulation of miR-107 decreased cell viability both in parental cells and resistance cells, decreased the expression of cofilin-1, enhanced ROS-induced cell apoptosis, and dose-dependently sensitized HDACi-R to HDACi. Further, miR-107 upregulation resulted in tumor cell disorganization in both HA22T and HDACi-R in a mice xenograft model. Our findings demonstrated that miR-107 downregulation leads to hepatocellular carcinoma cell resistance in HDACi via a cofilin-1-dependent molecular mechanism and ROS accumulation.