J Cancer 2019; 10(12):2706-2719. doi:10.7150/jca.31845

Research Paper

CBX2 Regulates Proliferation and Apoptosis via the Phosphorylation of YAP in Hepatocellular Carcinoma

Jiakai Mao1,*, Yu Tian1,2,*, Chengye Wang1, Keqiu Jiang1, Rui Li1, Yifan Yao1, Rixin Zhang1, Deguang Sun1, Rui Liang1, Zhenming Gao1, Qi Wang3✉, Liming Wang1✉

1. Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
2. Department of Vascular Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
3. Department of Pulmonary Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
*These authors have contributed equally to this work

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Citation:
Mao J, Tian Y, Wang C, Jiang K, Li R, Yao Y, Zhang R, Sun D, Liang R, Gao Z, Wang Q, Wang L. CBX2 Regulates Proliferation and Apoptosis via the Phosphorylation of YAP in Hepatocellular Carcinoma. J Cancer 2019; 10(12):2706-2719. doi:10.7150/jca.31845. Available from http://www.jcancer.org/v10p2706.htm

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Abstract

Chromobox 2 (CBX2), a chromobox family protein, is a crucial component of the polycomb group complex: polycomb repressive complex 1 (PRC1). Research on CBX2 as an oncogene has been published in recent years. However, the connection between CBX2 and hepatocellular carcinoma (HCC) has not been studied. In this article, based on the results of immunohistochemical (IHC) staining of HCC and adjacent liver tissue microarrays, we found that high CBX2 expression is associated with poor prognosis in HCC patients. The results of a CCK8 assay, a clonogenic survival assay and a nude mouse tumorigenicity assay showed that knockdown of CBX2 inhibited the proliferation of HCC cells. According to the results of Annexin V-FITC/propidium iodide (PI) staining-based fluorescence activated cell sorting (FACS) analysis, knockdown of CBX2 increased HCC cell apoptosis. Furthermore, the RNA-seq results revealed that knockdown of CBX2 inhibited the expression of WTIP, which is an inhibitor of the Hippo pathway. We used western blotting to validate the mechanism and discovered that knockdown of CBX2 increased the phosphorylation of YAP, which explains why knockdown of CBX2 inhibits proliferation and increases apoptosis in HCC cells. In conclusion, CBX2 could be a potential target for HCC anticancer treatment.

Keywords: Chromobox 2 (CBX2), Hepatocellular carcinoma (HCC), Hippo pathway, Yes-associated protein (YAP)