title: Aberrant histone methylation and the effect of Suv39H1 siRNA on gastric carcinoma.
abstract: The present study aimed to investigate the involvement of the Suv39H1 histone methyltransferase in the epigenetic changes in the euchromatic promoter in gastric carcinoma. We retrospectively analyzed the protein of Suv39H1 and tri-methylated histone H3 lysine 9 (H3K9) and histone H3 lysine 4 (H3K4) in 175 cases of gastric carcinoma by immunohistochemistry. Suv39H1 was depleted by siRNA, and cell apoptosis and cell proliferation were assessed by TUNEL and MTT assays, respectively. Histone methylated H3K9 and histone acetylated H3 and H4 were evaluated by western blotting. We found that the expression of Suv39H1 and tri-methylated H3K9 in gastric carcinoma was higher than that in benign gastric diseases (p<0.05). Tri-methylated H3K4 was similar in both tissue types (p>0.05). Both Suv39H1 and tri-methylated H3K9 were positively correlated with the degree of differentiation, depth of infiltration and lymphatic invasion (p<0.05) in gastric carcinoma. In addition, tri-methylated H3K9 was positively correlated with tumor stage, and node and metastatic statuses (p<0.05). Activation of Suv39H1 and overexpression of H3K9 tri-methylation may play an important role in tumorigenesis. They may be useful as a predictor for poor prognosis in gastric carcinoma. Silencing of the Suv39H1 gene decreased tri-methylated H3K9 and increased histone H3 acetylation, which caused activation of gene transcription, while there was no change in histone H4 acetylation. Depletion of Suv39H1 induced apoptosis and inhibited cell proliferation in the gastric cancer MGC803 cell line, while decreasing BCL-2, pro-caspase-9, pro-caspase-3 and C-myc. Suv39H1 may be a potential gene target for anti-gastric carcinoma therapy.
authors.affiliation: Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, P.R. China.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Cai
authors.affiliation: Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, P.R. China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Ma
authors.affiliation: Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, P.R. China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zou
authors.affiliation: United Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Xingsheng
authors.initials: X
authors.lastname: Chen
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3 / Q000096:biosynthesis; D049109:Cell Proliferation / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D006657:Histones; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C407843:SUV39H1 protein, human; D008780:Methyltransferases; D053148:Caspase 3