The role of vesicular overexpressed in cancer pro-survival protein 1 in hepatocellular carcinoma proliferation

Article type: Research Article

Authors: Fang, Zheping^{a; 1} | Wu, Linjun^{a; 1} | Dai, Haojiang^{a; 1} | Hu, Peng^a | Wang, Binfeng^a | Han, Qiuyue^a | Xu, Yongfu^a | Lv, Shangdong^a | Zhu, Yu^a | Gan, Meifu^b | Zhou, Weijie^c | Zhang, Wenlong^{d; *}

Affiliations: [a] Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China | [b] Department of Pathology, Enze Hospital, Wenzhou Medical University, Taizhou, Zhejiang, China | [c] Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China | [d] Department of Hepatobiliary Surgery, Enze Hospital, Wenzhou Medical University, Taizhou, Zhejiang, China

Correspondence: [*] Corresponding author: Wenlong Zhang, Department of Hepatobiliary Surgery, Enze Hospital, Wenzhou Medical University, No. 1 Tongyang Road, Tongyu, Luqiao, Taizhou, Zhejiang 318000, China. Tel.: +86 85199121; Fax: +86 85199615; %****␣cbm-28-cbm190574_temp.tex␣Line␣125␣**** E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: BACKGROUND: Recently, hepatocellular carcinoma (HCC) has been ranked as the second leading cause of cancer-associated death. However, the underlying molecular mechanisms of HCC progression remain unclear. Vesicular overexpressed in cancer pro-survival protein 1 (VOPP1) could be upregulated in a quantity of human cancers, including squamous cell carcinoma (SCC), gastric cancer, and glioblastoma. However, the precise functional mechanism of VOPP1 in HCC remains poorly understood. The present study aimed to investigate the role of VOPP1 in HCC proliferation. METHODS: Immunohistochemistry (IHC), Western blot and Reverse-transcription polymerase chain reaction (RT-PCR) were used to analyze the protein and mRNA expressions of VOPP1, mitogen-activated protein kinase (MAPK) 14, ribosomal protein S6 kinase β1 (RPS6KB1), cylindromatosis (CYLD) and Twist family bHLH transcription factor 1 (TWIST1). The cell proliferation and apoptosis were tested using Celigo cell imaging analyzer and annexin V-APC apoptosis detection kit respectively. Colony formation and tumor xenograft assays were performed to understand their roles in tumorigenicity. RESULTS: The expression of VOPP1 in HCC samples was higher than that in adjacent noncancerous tissues by immunohistochemistry. In addition, the down-regulation of VOPP1 using shRNA inhibited cell proliferation and tumour growth, and induced cell apoptosis in vitro and in vivo. Furthermore, VOPP1 silencing increased the expression of MAPK14 and RPS6KB1, indicating that the MAPK and mTOR signalling pathways might be involved in VOPP1-mediated cancer cell proliferation. CONCLUSION: The present data indicate that VOPP1 may play an important role in the progression of HCC by targeting the MAPK and mTOR signalling pathways, and that VOPP1 may potentially be a candidate as a novel molecular target for HCC therapy.

Keywords: VOPP1, hepatocellular carcinoma, proliferation, apoptosis

DOI: 10.3233/CBM-190574

Journal: Cancer Biomarkers, vol. 28, no. 1, pp. 9-20, 2020