title: Histone deacetylase HDAC4 promotes gastric cancer SGC-7901 cells progression via p21 repression.
abstract: Gastric cancer (GC) is one of the leading causes of cancer death in the world. The role of histone deacetylase 4 (HDAC4) in specific cell and tissue types has been identified. However, its biological roles in the development of gastric cancer remain largely unexplored. Quantitative real time PCR (qRT-PCR) and western blot were used to analyze the expression of HDAC4 in the clinical samples. siRNA and overexpression of HDAC4 and siRNA p21 were used to study functional effects in a proliferation, a colony formation, a adenosine 5'-triphosphate (ATP) assay and reactive oxygen species(ROS) generation, cell cycle, cell apoptosis rates, and autophagy assays. HDAC4 was up-regulated in gastric cancer tissues and several gastric cancer cell lines. The proliferation, colony formation ability and ATP level were enhanced in HDAC4 overexpression SGC-7901 cells, but inhibited in HDAC4 knockdown SGC-7901 cells. HDAC4 knockdown led to G0/G1 phase cell arrest and caused apoptosis and ROS increase. Moreover, HDAC4 was found to inhibit p21 expression in gastric cancer SGC-7901 cells. p21 knockdown dramatically attenuated cell proliferation inhibition, cell cycle arrest, cell apoptosis promotion and autophagy up-regulation in HDAC4-siRNA SGC-7901 cells. We demonstrated that HDAC4 promotes gastric cancer cell progression mediated through the repression of p21. Our results provide an experimental basis for understanding the pro-tumor mechanism of HDAC4 as treatment for gastric cancer.
authors.affiliation: Department of Colorectal and Anus Surgery, First Hospital, Jilin University, Changchun, P. R. China.
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Kang
authors.affiliation: The Tumor Research Institute of JiLin Province, Changchun, P. R. China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Colorectal and Anus Surgery, First Hospital, Jilin University, Changchun, P. R. China.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Zhang
authors.affiliation: Department of Colorectal and Anus Surgery, First Hospital, Jilin University, Changchun, P. R. China.
authors.forename: Jian-Tao
authors.initials: JT
authors.lastname: Zhang
authors.affiliation: Department of Colorectal and Anus Surgery, First Hospital, Jilin University, Changchun, P. R. China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Yuan
authors.affiliation: Department of Colorectal and Anus Surgery, First Hospital, Jilin University, Changchun, P. R. China.
authors.forename: Ping-Wei
authors.initials: PW
authors.lastname: Zhao
authors.affiliation: Department of Colorectal and Anus Surgery, First Hospital, Jilin University, Changchun, P. R. China.
authors.forename: Yu-Yang
authors.initials: YY
authors.lastname: Lin
authors.affiliation: Department of Colorectal and Anus Surgery, First Hospital, Jilin University, Changchun, P. R. China.
authors.forename: Sen
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Colorectal and Anus Surgery, First Hospital, Jilin University, Changchun, P. R. China.
authors.forename: Chen-Yao
authors.initials: CY
authors.lastname: Li
authors.affiliation: Department of Colorectal and Anus Surgery, First Hospital, Jilin University, Changchun, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D016022:Case-Control Studies; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D014410:Tumor Stem Cell Assay
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D000255:Adenosine Triphosphate; C400300:HDAC4 protein, human; D006655:Histone Deacetylases