The oncoprotein HBXIP up-regulates YAP through activation of transcription factor c-Myb to promote growth of liver cancer

Abstract The oncoprotein Yes-associated protein (YAP) in Hippo pathway plays crucial roles in the development of cancer. However, the mechanism of YAP regulation in cancer remains poorly understood. Here, we supposed that the oncoprotein hepatitis B X-interacting protein (HBXIP) might be involved in the modulation of YAP in liver cancer. Interestingly, our data showed that the expression levels of HBXIP were positively associated with those of YAP in clinical hepatocellular carcinoma (HCC) samples by immunohistochemistry (IHC) staining and real-time PCR assays. HBXIP was able to up-regulate YAP in hepatoma cells at the levels of promoter, mRNA and protein. Mechanistically, we identified that HBXIP up-regulated YAP through co-activating the transcription factor c-Myb in hepatoma cells. Functionally, silencing YAP abolished the proliferation of hepatoma cells mediated by HBXIP in vitro . Moreover, knockdown of YAP strongly blocked the HBXIP-enhanced tumor growth in mice. Thus, we conclude that HBXIP up-regulates YAP expression via activating transcription factor c-Myb to facilitate the growth of hepatoma cells. Our finding provides new insights into the mechanism of YAP regulation. Therapeutically, the oncoprotein HBXIP and YAP might serve as targets in liver cancer.