Mediator subunit 23 overexpression as a novel target for suppressing proliferation and tumorigenesis in hepatocellular carcinoma.

Yu Guo, Jing Wang, Hua Li, Wei Liu, Dong Chen, Kun Zhao, Xinjun Liang, Qi Zhang, Yang Yang, Guihua Chen

Journal of gastroenterology and hepatology 2015 Jun

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Hepatocellular carcinoma (HCC) is the fifth most frequent cancer in the world. However, the molecular mechanisms involved in HCC are still poorly understood. Here, we study the role of mediator subunit 23 (MED23), a component of the Mediator complex, in hepatocarcinogenesis. We detected MED23 expression in HCC samples by real-time polymerase chain reaction (PCR) and immunohistochemistry analysis. We also knocked down and overexpressed MED23 to explore its functional role in hepatoma cell growth. The cell cycle was examined by flow cytometry analysis, and protein expression was examined by Western blot. A xenograft mouse model was used to determine whether MED23 is involved in tumorigenesis. MED23 was frequently upregulated in human HCC tissues compared with paired adjacent non-tumorous liver tissues. The hepatoma cells also showed increased MED23 expression. MED23 knockdown inhibited hepatoma cell growth, whereas overexpression of MED23 promoted cell growth. Knockdown of MED23 induced a G1 to S phase arrest. Moreover, MED23 regulated the expression of p16(INK) (4a) (p16) and the phosphorylation of retinoblastoma protein (Rb). p16 was transcriptionally upregulated, and its promoter was demethylated. The G1 to S phase arrest induced by MED23 knockdown was aborted after p16 was silenced. Furthermore, MED23 knockdown suppressed tumorigenesis and regulated p16/Rb signaling in vivo. Taken together, our study suggests that MED23 plays an important role in hepatocarcinogenesis, and it may be a novel target for HCC therapy. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Citation

Yu Guo, Jing Wang, Hua Li, Wei Liu, Dong Chen, Kun Zhao, Xinjun Liang, Qi Zhang, Yang Yang, Guihua Chen. Mediator subunit 23 overexpression as a novel target for suppressing proliferation and tumorigenesis in hepatocellular carcinoma. Journal of gastroenterology and hepatology. 2015 Jun;30(6):1094-103