title: The Roles of miR-26, miR-29, and miR-203 in the Silencing of the Epigenetic Machinery during Melanocyte Transformation.
abstract: The epigenetic marks located throughout the genome exhibit great variation between normal and transformed cancer cells. While normal cells contain hypomethylated CpG islands near gene promoters and hypermethylated repetitive DNA, the opposite pattern is observed in cancer cells. Recently, it has been reported that alteration in the microenvironment of melanocyte cells, such as substrate adhesion blockade, results in the selection of anoikis-resistant cells, which have tumorigenic characteristics. Melanoma cells obtained through this model show an altered epigenetic pattern, which represents one of the first events during the melanocytes malignant transformation. Because microRNAs are involved in controlling components of the epigenetic machinery, the aim of this work was to evaluate the potential association between the expression of miR-203, miR-26, and miR-29 family members and the genes Dnmt3a, Dnmt3b, Mecp2, and Ezh2 during cells transformation. Our results show that microRNAs and their validated or predicted targets are inversely expressed, indicating that these molecules are involved in epigenetic reprogramming. We also show that miR-203 downregulates Dnmt3b in mouse melanocyte cells. In addition, treatment with 5-aza-CdR promotes the expression of miR-26 and miR-29 in a nonmetastatic melanoma cell line. Considering the occurrence of CpG islands near the miR-26 and miR-29 promoters, these data suggest that they might be epigenetically regulated in cancer.
authors.affiliation: Department of Biochemistry, Federal University of Sao Paulo, 04044-020 Sao Paulo, SP, Brazil ; Department of Genetics and Evolutionary Biology, University of Sao Paulo, 05508-090 Sao Paulo, SP, Brazil.
authors.forename: Cláudia Regina
authors.initials: CR
authors.lastname: Gasque Schoof
authors.affiliation: Department of Health Sciences, University of Genoa, 16132 Genoa, Italy ; IRCCS AOU San Martino IST, 16132 Genoa, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Izzotti
authors.affiliation: Department of Pharmacology, Federal University of Sao Paulo, 04039-032 Sao Paulo, SP, Brazil.
authors.forename: Miriam Galvonas
authors.initials: MG
authors.lastname: Jasiulionis
authors.affiliation: Department of Biochemistry, Federal University of Sao Paulo, 04044-020 Sao Paulo, SP, Brazil ; Department of Genetics and Evolutionary Biology, University of Sao Paulo, 05508-090 Sao Paulo, SP, Brazil.
authors.forename: Luciana Dos Reis
authors.initials: Ldos R
authors.lastname: Vasques
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D018899:CpG Islands / Q000187:drug effects / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics*; D057890:Epigenomics / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D020868:Gene Silencing / Q000187:drug effects / Q000502:physiology*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism*; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics
chemical_list: C575934:MIRN203 microRNA, mouse; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D001374:Azacitidine