title: Epigenetic regulation of microRNA expression in Hodgkin lymphoma.
abstract: Epigenetic mechanisms are crucial for the inactivation of key genes related to the survival of Hodgkin lymphoma (HL) cells, and methylation is a frequent epigenetic mechanism of microRNA silencing. We have examined the methylation-induced silencing of tumor suppressor microRNAs in HL cell lines and confirmed our results in patient lymph nodes. In addition, we evaluated the in vitro effectiveness of 5-aza-2-deoxycytidine (5-Aza-dC) in HL cell lines. Ten microRNAs containing CpG islands in their promoter region were re-expressed in both the L-428 and L-1236 cell lines. Interestingly, miR-34a and miR-203, both known tumor suppressor microRNAs, were found to be methylated in cell lines and in patient samples. 5-Aza-dC treatment resulted in a dose-dependent antiproliferative effect at 72 h in all the HL cell lines. In summary, 5-Aza-dC treatment of HL cell lines inhibits proliferation at high doses and produces re-expression of the tumor suppressor microRNAs at low-intermediate doses.
authors.affiliation: a Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS , Barcelona , Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Navarro
authors.affiliation: a Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS , Barcelona , Spain.
authors.forename: Tania
authors.initials: T
authors.lastname: Díaz
authors.affiliation: a Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS , Barcelona , Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Cordeiro
authors.affiliation: b Hematology Department, Hospital Clinic Barcelona , Barcelona , Spain.
authors.forename: Marina Díaz
authors.initials: MD
authors.lastname: Beyá
authors.affiliation: c Laboratory of Translational Hematology, Hospital Clinic, IDIBAPS , Barcelona , Spain.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ferrer
authors.affiliation: a Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS , Barcelona , Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Fuster
authors.affiliation: d Hematopathology Section, Hospital Clinic, IDIBAPS , Barcelona , Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Martinez
authors.affiliation: a Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS , Barcelona , Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Monzó
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019175:DNA Methylation; D000077209:Decitabine; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D000077209:Decitabine; D001374:Azacitidine
keywords: Lymphoma and Hodgkin disease; cell lines and animal models; chemotherapeutic approaches