The role of ankyrin repeats and SOCS box protein 4 (ASB4) in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC)is one of the commonly diagnosed cancers in the world. Most patients have poor prognosis due to late detection of disease. Ankyrin repeat and suppressor of cytokine signaling box protein 4(ASB4), as a member of the ASB family, possesses two domains, ankyrin repeat (AR) and suppressor of cytokine signaling (SOCS)box, which are responsible for recruiting the target proteins for proteasomal degradation. Previous study has demonstrated high expression level of ASB4 in metastatic HCC cells, implicating the properties of ASB4 in cancer invasiveness. With this hypothesis, various experiments were performed in this research project to elucidate the functional roles of ASB4 in HCC cells. The aim of this study is to characterize the roles of ASB4 in HCC by manipulating its expression level in HCC cell lines through gene knockdown and over-expression. Altering the level of ASB4 in HCC cells resulted in no significant effects on the cell proliferation rates. However, ASB4 was demonstrated to promote migration and invasion properties of HCC cells, as suppression of its level led to slower migration and made cells less invasive. Opposite effects on cell migration and invasion were observed when ASB4 was ectopically expressed. Regarding the regulatory mechanism of ASB4, miR-200a was demonstrated to be a negative regulator for ASB4. In summary, ASB4 is probably involved in the migration and invasion properties of HCC cells, and also, being regulated by miR-200a.