Transcriptional regulation of miR-10a/b by TWIST-1 in myelodysplastic syndromes.

Publication Type:

Journal Article

Source:

Haematologica, Volume 98, Issue 3, p.414 (2013)

Keywords:

2013, Cell Processing Core Facility, Center-Authored Paper, Clinical Research Division, Flow Cytometry Core Facility, October 2012, Research Trials Office Core Facility - Biostatistics Service

Abstract:

Abstract The transcription factor TWIST-1 is up-regulated in CD34+ cells in myelodysplastic syndrome and is involved in resistance to apoptosis. There is evidence that TWIST-1 affects apoptosis via microRNAs (miRs). Expression of miRs was determined in myeloid cell lines and primary CD34+ marrow cells from patients with MDS and healthy donors using nanostring/array and validated by RT-PCR. Expression levels of miR10a and miR10b were significantly higher in CD34+ marrow cells from 28 patients with myelodysplastic syndrome than in CD34+ cells from healthy donors (p=0.05 and p=0.012, respectively). Levels of miR10a/b correlated with TWIST-1 miR levels in CD34+ myelodysplastic marrow cells (miR10a, R=+0.69, p<0.0001; miR10b, R=+0.56, p=0.0008). Inhibition of miR10a/10b in clonal cells interfered with proliferation and enhanced sensitivity to apoptosis, which involved NF-κB-dependent p53 activation. These data support a role for miR10a/10b in the regulation of apoptosis in myelodysplastic syndrome and suggest the TWIST-1/miR10a/b-axis as a therapeutic target in myelodysplastic syndrome. Keywords miR10a; miR10b; p53; TWIST-1; NF-κB; myelodysplastic syndrome.