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

Hsin An Chen, Chi Cheng Li, Yu Jung Lin, Tso Fu Wang, Ming Cheng Chen, Yen Hao Su, Yu Lan Yeh, V. Vijaya Padma, Po Hsiang Liao, Chih Yang Huang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)12046-12057
Number of pages12
JournalAging
Volume13
Issue number8
DOIs
Publication statusPublished - 2021

Keywords

  • chemosensitivity
  • drug resistance
  • hepatocellular carcinoma
  • miR-107

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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