title: The inhibition of histone deacetylase 8 suppresses proliferation and inhibits apoptosis in gastric adenocarcinoma.
abstract: Histone deacetylase 8 (HDAC8), a unique member of class I HDACs, shows remarkable correlation with advanced disease stage. The depletion of HDAC8 leads to inhibition of proliferation, apoptosis and cell cycle arrest in multiple malignant tumors. However, little is known about the contribution of HDAC8 to the tumorigenesis of gastric cancer (GC). The present study investigated expression of HDAC8 in GC cell lines and tissues, and the roles of HDAC8 inhibition in the proliferation, cell cycle and apoptosis of gastric cancer cells and explored the potential mechanisms. In the present study, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry were used to examine the mRNA and protein expression of HDAC8 in GC cell lines and tissues. Then, the correlation between the clinicopathological parameters and the expression of HDAC8 was assessed. Finally, siRNA transfection and HDAC8 plasmid was performed to explore the functions of HDAC8 in GC progression in vitro. We found that the expression of HDAC8 was significantly upregulated both in GC cell lines and tumor tissues compared to human normal gastric epithelial cell, GES-1 and matched non-tumor tissues. Furthermore, depletion of HDAC8 remarkably inhibited GC cell proliferation, increased the apoptosis rate and G0/G1 phase percentage in vitro. Western blotting showed that the expression of protein promoting apoptosis such as, Bmf, activated caspase-3, caspase-6 were elevated following HDAC8 depletion. Our data exhibited an important role of HDAC8 in promoting gastric cancer tumorigenesis and identify this HDAC8 as a potential therapeutic target for the treatment of gastric cancer.
authors.affiliation: Department of Oncology, Τhe First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Oncology, Τhe First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, Τhe First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Po
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Oncology, Τhe First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Ruina
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Oncology, Τhe First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Oncology, Τhe First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Oncology, Τhe First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Guangping
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D016193:G1 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D012097:Repressor Proteins; C409470:HDAC8 protein, human; D006655:Histone Deacetylases