Ebp1 p48 promotes oncogenic properties in hepatocellular carcinoma through p38 MAPK/HIF1α activation and p53 downregulation

Abstract The ErbB3 binding protein 1 (Ebp1) has been reported in several cancers, in which it can act as either a pro‐oncogenic regulator or a tumor suppressor. However, the biological function and molecular mechanism of Ebp1 p48 in hepatocellular carcinoma (HCC) remain unclear. Here, we report that the long isoform of Ebp1, p48, is highly expressed in HCC tissues compared with normal tissues. Ebp1 p48 expression was correlated with the tumor size in HCC patients. Silencing Ebp1 p48 by transduction with lentiviral shEbp1 dramatically reduced the proliferation rate, soft agar colony generation, and tumor formation in vivo. We further demonstrated that Ebp1 p48 knockdown resulted in decreased p38 phosphorylation, which subsequently reduced hypoxia‐inducible factor 1α (HIF1α) expression. Moreover, Ebp1 p48 knockdown led to an upregulation of p53 expression through MDM2 downregulation. Taken together, these results suggest that the Ebp1/p38/HIF1α signaling pathway and the Ebp1‐mediated downregulation of p53 are involved in hepatocarcinogenesis. Therefore, Ebp1 and its downstream signaling pathways may be promising therapeutic targets of HCC.