RNA-binding motif protein 43 (RBM43) suppresses hepatocellular carcinoma progression through modulation of cyclin B1 expression.

RNA-binding proteins play key roles in the posttranscriptional regulation of mRNA during cancer progression. Here, we show that RNA-binding motif protein 43 (RBM43) is significantly downregulated in human tumors, and its low expression is correlated with poor prognosis in patients with HCC. Overexpression of RBM43 suppressed cell proliferation in culture and resulted in the growth arrest of tumor xenografts, whereas downregulating RBM43 played an opposite role. We have also demonstrated that overexpression or knockdown of RBM43 affects the cell-cycle progression of liver cancer cells. Mechanistically, RBM43 directly associated with the 3'UTR of Cyclin B1 mRNA and regulated its expression. Moreover, loss of Rbm43 in mice promoted liver carcinogenesis and HCC development after diethylnitrosamine (DEN)-carbon tetrachloride (CCl) treatment. Taken together, our data indicate that RBM43 is a tumor suppressor that controls the cell cycle through modulation of Cyclin B1 expression, providing evidence that RBM43 is particularly important in HCC.