title: DNA demethylation is superior to histone acetylation for reactivating cancer-associated genes in ovarian cancer cells.
abstract: To investigate the contributions of histone H3 lysine 9 acetylation and DNA methylation to p16, hMLH1 and MGMT silencing in ovarian cancer cells, we treated three ovarian cancer cell lines with Trichostatin A (TSA) and 5-aza-2'-deoxycytidine and examined the status of mRNA expression, DNA methylation and histone H3 lysine 9 acetylation at the promoter of p16, hMLH1 and MGMT. The results showed that the hypermethylated silenced tumor-related genes in the ovarian cancer cells were characterized by hypoacetylated histone H3 lysine 9. Treatment with TSA resulted in the increase of histone H3 lysine 9 acetylation at the hypermethylated promoter, but with little effects on gene expression. TSA did not contribute to DNA demethylation. 5-aza-2'-deoxycytidine treatment caused DNA demethylation, increased histone H3 lysine 9 acetylation at the hypermethylated promoter and resulted in reactivation of p16, hMLH1 and MGMT. Combined treatments synergistically increased histone H3 lysine 9 acetylation accompanied by the re-expression of the hypermethylated genes. To conclude, in ovarian cancer cells, DNA methylation and histone deacetylation act synergistically for the silencing of cancer-associated genes. DNA demethylation is superior to histone acetylation for reactivating cancer-associated genes.
authors.affiliation: Department of Gynecology, First Affiliated Hospital, China Medical University, Shenyang, PR China. mcflovesb@gmail.com
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Meng
authors.forename: Bo
authors.initials: B
authors.lastname: Su
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D000077209:Decitabine; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008239:Lysine / Q000378:metabolism; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000964:Antimetabolites, Antineoplastic; D019941:Cyclin-Dependent Kinase Inhibitor p16; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C012589:trichostatin A; D000077209:Decitabine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes; D008239:Lysine; D001374:Azacitidine