CSN5 Promotes Hepatocellular Carcinoma Progression by SCARA5 Inhibition Through Suppressing β-Catenin Ubiquitination.

Abstract

Increasing evidence has suggested that E3 Ubiquitin LigaseCSN5 is a newly characterized oncogene involved in various types of cancer. Scavenger receptor class A member 5 (SCARA5) is an important regulator of biological processes in cancer cells. However, the roles and relationship of CSN5 and SCARA5 in hepatocellular carcinoma (HCC) remain unclear. We used RT-PCR, Western blot, and immunohistochemistry to measure CSN5 and SCARA5 expression in HCC tissues and corresponding non-tumor tissues. The CSN5 gene was overexpressed or silenced with lentiviral vectors in HCC cells. Cell proliferation was measured using CCK8 assay. And, the cell migration and invasion were analyzed by transwell assay. We found that the expressions of CSN5 and SCARA5 are inversely correlated in HCC tissues, and CSN5 expression levels were negatively correlated with the levels of SCARA5 in various HCC cells. Furthermore, we found that high level of CSN5 expression correlated closely with tumor TNM stage, tumor size, and venous metastasis, but low level of SCARA5 expression correlated closely with tumor TNM stage, tumor size, and venous metastasis. Additionally, survival of patients with lower expression of CNS5 was significantly better than that of higher expression group, but the survival of patients with higher expression of SCARA5 was significantly better than that of lower expression group. Moreover, knockdown of CSN5 increased SCARA5 expression and inhibited the proliferation and metastasis of HCC cells in vitro and in vivo. Finally, we found that CSN5 regulated SCARA5 expression by modulating β-catenin. Mechanistically, our results indicate that CSN5 can decrease β-catenin ubiquitination to enhance the protein expression of SCARA5 in HCC cells. Our data identified CSN5 as a critical oncoprotein involved in progression of HCC cells, which could serve as a potential therapeutic target in HCC patients.