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.

中文翻译：

---

Ebp1 p48通过激活p38 MAPK /HIF1α和下调p53来促进肝细胞癌的致癌性

ErbB3结合蛋白1（Ebp1）在几种癌症中都有报道，在其中它既可以作为致癌调节剂，也可以作为抑癌剂。然而，Ebp1 p48在肝细胞癌（HCC）中的生物学功能和分子机制仍不清楚。在这里，我们报告说，与正常组织相比，Ebp1的长同种型p48在HCC组织中高表达。Ebp1 p48表达与HCC患者的肿瘤大小相关。通过慢病毒shEbp1的转导沉默Ebp1 p48，可显着降低体内的增殖率，琼脂菌落的产生和肿瘤的形成。我们进一步证明，Ebp1 p48的敲低导致p38磷酸化水平的降低，从而降低了缺氧诱导因子1α（HIF1α）的表达。而且，Ebp1 p48抑制通过MDM2下调导致p53表达上调。综上所述，这些结果表明，Ebp1 / p38 /HIF1α信号通路和Ebp1介导的p53下调与肝癌的发生有关。因此，Ebp1及其下游信号通路可能是有希望的肝癌治疗靶标。