title: Methylation of promoters of microRNAs and their host genes in myelodysplastic syndromes.
abstract: Myelodysplastic syndromes (MDS) are a group of hematopoietic malignancies characterized by ineffective hematopoiesis. Recently, we identified MDS-associated microRNAs (miRNAs) that are down-regulated in MDS. This study examines possible explanations for that observed down-regulation of miRNA expression in MDS. Since genomic losses are insufficient to explain the down-regulation of all our MDS-associated miRNAs, we explored other avenues. We demonstrate that these miRNAs are predominantly intragenic, and that, in many cases, they and their host genes are expressed in a similar pattern during myeloid maturation, suggesting their co-regulation. This co-regulation is further supported by the down-regulation of several of the host genes in MDS and increased methylation of the shared promoters of several miRNAs and their respective host genes. These studies identify a role of hypermethylation of miRNA promoters in the down-regulation of MDS-associated miRNAs, unifying research on miRNAs in MDS and epigenetic regulation in MDS into a common pathway.
authors.affiliation: Department of Pathology, Immunology, and Microbiology.
authors.forename: Begum
authors.initials: B
authors.lastname: Erdogan
authors.forename: Amma
authors.initials: A
authors.lastname: Bosompem
authors.forename: Dunfa
authors.initials: D
authors.lastname: Peng
authors.forename: Leng
authors.initials: L
authors.lastname: Han
authors.forename: Emily
authors.initials: E
authors.lastname: Smith
authors.forename: Mija E
authors.initials: ME
authors.lastname: Kennedy
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Alford
authors.forename: Huiyun
authors.initials: H
authors.lastname: Wu
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Mosse
authors.forename: Wael
authors.initials: W
authors.lastname: El-Rifai
authors.forename: Annette S
authors.initials: AS
authors.lastname: Kim
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D018899:CpG Islands; D019175:DNA Methylation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D011401:Promoter Regions, Genetic; D059467:Transcriptome; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D035683:MicroRNAs; D014212:Tretinoin
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