Aging
Navigate
Submit an Article
Research Paper|Volume 14, Issue 14|pp 5710—5726

Sofosbuvir induces gene expression for promoting cell proliferation and migration of hepatocellular carcinoma cells

Wei-Lun Tsai1,2,3,4, Jin-Shiung Cheng2, Pei-Feng Liu5,6, Tsung-Hsien Chang7, Wei-Chih Sun2, Wen-Chi Chen2, Chih-Wen Shu8
  • 1Division of General Internal Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
  • 2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
  • 3School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  • 4School of Nursing, Fooyin University, Kaohsiung, Taiwan
  • 5Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 6Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
  • 7Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan
  • 8Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
Received: June 5, 2021Accepted: May 13, 2022Published: July 12, 2022
https://doi.org/10.18632/aging.204170

Copyright: © 2022 Tsai 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

Direct-acting antivirals (DAAs) have achieved a sustained virological response (SVR) rate of 95–99% in treating HCV. Several studies suggested that treatment with sofosbuvir (SOF), one type of DAAs, may be associated with increased risk of developing HCC. The aim of this study is to investigate the potential mechanisms of SOF on the development of HCC. OR-6 (harboring full-length genotype 1b HCV) and Huh 7.5.1 cells were used to examine the effects of SOF on cell proliferation and migration of HCC cells. SOF-upregulated genes in OR-6 cells were inspected using next generation sequencing (NGS)and the clinical significance of these candidate genes was analyzed using The Cancer Genome Atlas (TCGA) database. We found that SOF increased cell proliferation and cell migration in OR-6 and Huh 7.5.1 cells. Several SOF-upregulated genes screened from NGS were confirmed by real-time PCR in OR-6 cells. Among these genes, PHOSPHO2, KLHL23, TRIM39, TSNAX-DISC1 and RPP21 expression were significantly elevated in the tumor tissues compared with the non-tumor tissues of HCC according to TCGA database. High expression of PHOSPHO2 and RPP21 was associated with poor overall survival of HCC patients. Moreover, knockdown of PHOSPHO2-KLHL23, TSNAX-DISC1, TRIM39 and RPP21 diminished cell proliferation and migration increased by SOF in OR-6 and Huh 7.5.1 cells. In conclusion, SOF-upregulated genes promoted HCC cell proliferation and migration, which might be associated with the development of HCC.