title: 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.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Runping
authors.initials: R
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Weiying
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, People's Republic of China. Electronic address: zhangxd@nankai.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, People's Republic of China. Electronic address: yelihong@nankai.edu.cn.
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D047368:Tumor Burden; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C110719:LAMTOR5 protein, human; D010750:Phosphoproteins; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human
keywords: HBXIP; Liver cancer; Proliferation; YAP; c-Myb