Research Paper Volume 14, Issue 14 pp 5710—5726
Sofosbuvir induces gene expression for promoting cell proliferation and migration of hepatocellular carcinoma cells
- 1 Division of General Internal Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- 2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- 3 School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- 4 School of Nursing, Fooyin University, Kaohsiung, Taiwan
- 5 Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan
- 6 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- 7 Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan
- 8 Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
Received: June 5, 2021 Accepted: May 13, 2022 Published: July 12, 2022https://doi.org/10.18632/aging.204170
How to Cite
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.
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.