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.
Original language | English (US) |
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Pages (from-to) | 2720-2727 |
Number of pages | 8 |
Journal | Leukemia and Lymphoma |
Volume | 54 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2013 |
Keywords
- Host genes
- Hypermethylation
- MicroRNAs
- Myelodysplastic syndrome
- Myeloid maturation
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research