Lentivirus-mediated overexpression of HSDL2 suppresses cell proliferation and induces apoptosis in cholangiocarcinoma
Authors Zhang DY, Liu Z, Lu Z, Sun WL, Ma X, Zhang P, Wu BQ, Cui PY
Received 5 June 2018
Accepted for publication 28 August 2018
Published 17 October 2018 Volume 2018:11 Pages 7133—7142
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 2
Editor who approved publication: Dr William Cho
Deng-Yong Zhang,1 Zhong Liu,1 Zheng Lu,1 Wan-Liang Sun,1 Xiang Ma,1 Pei Zhang,2 Bin-Quan Wu,1 Pei-Yuan Cui1
1Department of General Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui, People’s Republic of China; 2Department of Pharmacy, Bengbu Medical College, Bengbu 233000, Anhui, People’s Republic of China
Background: Cholangiocarcinoma (CCA) is a malignant tumor of the bile duct epithelium, including intrahepatic, perihilar, and distal CCA based on anatomical location. Hydroxysteroid dehydrogenase-like 2 (HSDL2) belongs to the SDR subfamily of oxidoreductases, and it is involved in glioma oncogenesis, as it can promote cell proliferation and inhibit cell apoptosis. The purpose of this study was to explore the underlying molecular mechanisms of HSDL2 in the process of CCA.
Methods: HSDL2 expression levels were observed in CCA and adjacent (normal control) tissues by analyzing data from The Cancer Genome Atlas and Gene Expression Omnibus databases. A receiver operating characteristic curve analysis was carried out. In vitro, we overexpressed HSDL2 in RBE cells (a human CCA cell line) using a stable lentivirus-mediated transduction strategy. We then used quantitative real-time-PCR and Western blotting methods to detect the efficiency of HSDL2 overexpression. Cell proliferation was assessed using a Celigo Image Cytometer, MTT assays, and the expression of PCNA. Cell apoptosis was assessed by flow cytometry analysis, caspase3/7 activity, and the expression of the apoptotic markers BCL-2 and BAX.
Results: We observed a downregulation of HSDL2 in CCA tissues based on The Cancer Genome Atlas and Gene Expression Omnibus data analysis. The receiver operating characteristic curve analysis showed that HSDL2 could be an excellent efficacy biomarker for CCA. In vitro, HSDL2 overexpression largely suppressed the proliferation of RBE cells. In addition, apoptosis was induced by HSDL2 overexpression.
Conclusion: The results of the data analysis indicated that, compared with adjacent tissues, HSDL2 was downregulated in CCA tissues, and overexpressing HSDL2 in CCA cells suppressed growth and proliferation, which involved activating apoptosis. This helps to understand the underlying HSDL2-related molecular mechanisms in the process of CCA.
Keywords: cholangiocarcinoma, CCA, HSDL2, lentivirus, proliferation, apoptosis
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