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Mediator subunit 23 overexpression as a novel target for suppressing proliferation and tumorigenesis in hepatocellular carcinoma
Author(s) -
Guo Yu,
Wang Jing,
Li Hua,
Liu Wei,
Chen Dong,
Zhao Kun,
Liang Xinjun,
Zhang Qi,
Yang Yang,
Chen Guihua
Publication year - 2015
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12923
Subject(s) - gene knockdown , carcinogenesis , cancer research , cell growth , cell cycle , downregulation and upregulation , hepatocellular carcinoma , western blot , biology , flow cytometry , cell cycle checkpoint , retinoblastoma , cell , microbiology and biotechnology , cancer , cell culture , gene , biochemistry , genetics
Background and Aim 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 M ediator complex, in hepatocarcinogenesis. Methods 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 W estern blot. A xenograft mouse model was used to determine whether MED23 is involved in tumorigenesis. Results 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 G 1 to S phase arrest. Moreover, MED23 regulated the expression of p16 INK 4a (p16) and the phosphorylation of retinoblastoma protein ( R b). p16 was transcriptionally upregulated, and its promoter was demethylated. The G 1 to S phase arrest induced by MED23 knockdown was aborted after p16 was silenced. Furthermore, MED23 knockdown suppressed tumorigenesis and regulated p16/ R b signaling in vivo . Conclusions Taken together, our study suggests that MED23 plays an important role in hepatocarcinogenesis, and it may be a novel target for HCC therapy.