J Cancer 2017; 8(18):3812-3827. doi:10.7150/jca.20775
Overexpression of SMOC2 Attenuates the Tumorigenicity of Hepatocellular Carcinoma Cells and Is Associated With a Positive Postoperative Prognosis in Human Hepatocellular Carcinoma
1. State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong province, 510060, China;
2. Huadu District People's Hospital of Guangzhou, Southern Medical University, Guangzhou, Guangdong province, 510800, China;
3. Department of Epidemiology and Health Statistics, Guangdong Pharmaceutical University, Guangzhou, Guangdong province, 510010, China;
4. Department of Health Service Management, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong province, 510006, China.
Xu-Qiong Huang and Zi-Qi Zhou contributed equally to this work.
Huang XQ, Zhou ZQ, Zhang XF, Chen CL, Tang Y, Zhu Q, Zhang JH, Xia JC. Overexpression of SMOC2 Attenuates the Tumorigenicity of Hepatocellular Carcinoma Cells and Is Associated With a Positive Postoperative Prognosis in Human Hepatocellular Carcinoma. J Cancer 2017; 8(18):3812-3827. doi:10.7150/jca.20775. Available from http://www.jcancer.org/v08p3812.htm
Secreted modular calcium binding protein-2 (SMOC2), a recently identified matricellular protein that belongs to the SPARC protein family, has been reported to be downregulated in various cancers. The purpose of this study was to investigate the clinical significance and biological function of SMOC2 in human hepatocellular carcinoma. Real-time quantitative PCR and western blotting analyses revealed that SMOC2 mRNA and protein levels were significantly downregulated in human HCC tissues compared to the matched adjacent normal tissues. Clinicopathological analysis indicated that SMOC2 expression was significantly associated with tumor size, number of tumors, tumor-node-metastasis (TNM) stage and distant metastasis. Kaplan-Meier survival analysis showed that high tumor SMOC2 expression was associated with improved overall survival and disease-free survival in patients with HCC. Functional analyses (cell proliferation and colony formation assays, cell migration and invasion assays, cell cycle and apoptosis assays) demonstrated that stable overexpression of SMOC2 using a lentiviral vector significantly inhibited cell proliferation, colony formation, migration and invasion, and induced G0/G1 phase arrest in HCC cells in vitro. In addition, experiments with a mouse model revealed the suppressed effect of SMOC2 on HCC tumorigenicity and metastases in vivo. These results suggest that SMOC2 functions as a tumor suppressor during the development of HCC and may represent an effective prognostic factor and novel therapeutic target for HCC.
Keywords: SMOC2, hepatocellular carcinoma, prognosis, tumor suppressor.