title: Epigenetic regulation of microRNA expression in renal cell carcinoma.
abstract: The underlying mechanisms of microRNA deregulation in cancer cells include epigenetic modifications, which play a crucial role in carcinogenesis. We demonstrate that numerous microRNAs are induced in renal cell carcinoma cell lines after treatment with inhibitors of the DNA-methyltransferase (5-aza-2'-deoxycytidine) and the histone-deacetylase (suberoylanilide hydroxamic acid). We provide evidence that enrichment of H3 and H3K18 acetylation at the miR-9 promoter is causative for re-expression, while DNA hypermethylation remains unchanged. Our experiments show that the treatment with the epigenetic drugs causes re-expression of silenced microRNAs with putative tumor suppressive function in ccRCC cell lines.
authors.affiliation: Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. miriam.schiffgen@gmx.de
authors.forename: Miriam
authors.initials: M
authors.lastname: Schiffgen
authors.forename: Doris H
authors.initials: DH
authors.lastname: Schmidt
authors.forename: Alexander
authors.initials: A
authors.lastname: von Rücker
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000378:metabolism; D000077209:Decitabine; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D000077337:Vorinostat
chemical_list: D006657:Histones; D006877:Hydroxamic Acids; D035683:MicroRNAs; D000077337:Vorinostat; D012313:RNA; D000077209:Decitabine; D015254:DNA Modification Methylases; D006655:Histone Deacetylases; D001374:Azacitidine