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) |
|---|---|
| Pages (from-to) | 2720-2727 |
| Number of pages | 8 |
| Journal | Leukemia and Lymphoma |
| Volume | 54 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2013 |
| Externally published | Yes |
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Keywords
- Host genes
- Hypermethylation
- MicroRNAs
- Myelodysplastic syndrome
- Myeloid maturation
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research
Cite this
Methylation of promoters of microRNAs and their host genes in myelodysplastic syndromes. / Erdogan, Begum; Bosompem, Amma; Peng, Dunfa; Han, Leng; Smith, Emily; Kennedy, Mija E.; Alford, Catherine E.; Wu, Huiyun; Zhao, Zhongming; Mosse, Claudio A.; El-Rifai, Wael; Kim, Annette S.
In: Leukemia and Lymphoma, Vol. 54, No. 12, 01.12.2013, p. 2720-2727.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Methylation of promoters of microRNAs and their host genes in myelodysplastic syndromes
AU - Erdogan, Begum
AU - Bosompem, Amma
AU - Peng, Dunfa
AU - Han, Leng
AU - Smith, Emily
AU - Kennedy, Mija E.
AU - Alford, Catherine E.
AU - Wu, Huiyun
AU - Zhao, Zhongming
AU - Mosse, Claudio A.
AU - El-Rifai, Wael
AU - Kim, Annette S.
PY - 2013/12/1
Y1 - 2013/12/1
N2 - 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.
AB - 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.
KW - Host genes
KW - Hypermethylation
KW - MicroRNAs
KW - Myelodysplastic syndrome
KW - Myeloid maturation
UR - http://www.scopus.com/inward/record.url?scp=84885010257&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885010257&partnerID=8YFLogxK
U2 - 10.3109/10428194.2013.790542
DO - 10.3109/10428194.2013.790542
M3 - Article
C2 - 23547841
AN - SCOPUS:84885010257
VL - 54
SP - 2720
EP - 2727
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
SN - 1042-8194
IS - 12
ER -