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

Mao, Jiakai; Tian, Yu; Wang, Chengye; Jiang, Keqiu; Li, Rui; Yao, Yifan; Zhang, Rixin; Sun, Deguang; Liang, Rui; Gao, Zhenming; Wang, Qi; Wang, Liming

doi:10.7150/jca.31845

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

Research Paper

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

Jiakai Mao^1,*, Yu Tian^1,2,*, Chengye Wang¹, Keqiu Jiang¹, Rui Li¹, Yifan Yao¹, Rixin Zhang¹, Deguang Sun¹, Rui Liang¹, Zhenming Gao¹, Qi Wang^3✉, Liming Wang^1✉

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

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. https://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)

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APA

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

ACS

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.

NLM

CSE

Mao J, Tian Y, Wang C, Jiang K, Li R, Yao Y, Zhang R, Sun D, Liang R, Gao Z, Wang Q, Wang L. 2019. CBX2 Regulates Proliferation and Apoptosis via the Phosphorylation of YAP in Hepatocellular Carcinoma. J Cancer. 10(12):2706-2719.

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