Role of RBM3 in the regulation of cell proliferation in hepatocellular carcinoma

Abstract

RNA binding motif protein 3 (RBM3) has been shown to be upregulated in several types of human tumors. Using tissue microarrays and immunohistochemistry, we showed here that both nuclear and cytoplasmic RBM3 expression levels were higher in hepatocellular carcinoma (HCC) tissues than in adjacent non-tumorous tissues. High nuclear RBM3 was found to be correlated with larger tumor size (P = 0.030), high serum AFP levels (P = 0.011), and advanced Edmonson grading (P = 0.006). Cytoplasmic RBM3 was associated with advanced Edmonson grading (P = 0.003). Kaplan-Meier survival analysis revealed that, although not statistically significant, there was a trend toward shortened overall survival in the subset of HCC patients with high RBM3 expression (both nuclear and cytoplasmic). In addition, we found that RBM3 could promote YAP1 expression in HCC cells. Moreover, we found that YAP1 played an essential part in RBM3-induced proliferation of HCC cells. Furthermore, we demonstrated that Verteporfin, a YAP1 inhibitor, could repress RBM3-induced proliferation of HCC cells. Our findings provide a new experimental basis for further understanding of the possible role of RBM3-YAP1 in the regulation of HCC proliferation.

Keywords: Hepatocellular carcinoma; Immunohistochemistry; Proliferation; RBM3; YAP1.