RCC2 contributes to tumor invasion and chemoresistance to cisplatin in hepatocellular carcinoma.

ABSTRACT

Tumor metastasis and chemoresistance are the main causes of treatment failure and high mortality in hepatocellular carcinoma (HCC). Therefore, it is critical to clarify the biological action and potential mechanisms in HCC cells to develop novel therapeutics. The regulator of chromosome condensation 2 (RCC2), a component of the chromosomal passenger complex, was shown to have important roles in tumor development and radio-chemotherapy resistance. However, its role in the aggressive phenotypes and cisplatin (DDP)-resistance of HCC is not known. Therefore, this study aimed to investigate the role of RCC2 in HCC pathogenesis. Interestingly, we found that RCC2 was upregulated in HCC patient specimens and HCC cell lines and was correlated with the pathological grade of HCC. To evaluate the function of RCC2 in HCC cell, lentivirus vector-based shRNAs were transfected into HCC cells. Silencing RCC2 inhibited the HCC cell proliferation, migration, invasion, and increased the apoptosis rate upon DDP treatment. Further analysis showed that RCC2-mediated downregulation of the expression of survival proteins occurred via the AKT and Bcl2 pathways. Our results suggest that RCC2 might act as an oncogenic protein promoting metastatic behaviors and cisplatin resistance in HCC cells, and thereby could be a potential prognostic biomarker and therapeutic target for HCC.