title: Transcriptional regulation of miR-10a/b by TWIST-1 in myelodysplastic syndromes.
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 myelodysplastic syndrome and healthy donors using NanoString/array and validated by real-time-polymerase chain reaction. 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.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: ChunKang
authors.initials: C
authors.lastname: Chang
authors.forename: John
authors.initials: J
authors.lastname: Byon
authors.forename: Thalia
authors.initials: T
authors.lastname: Papayannopoulou
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.forename: A Mario
authors.initials: AM
authors.lastname: Marcondes
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D001853:Bone Marrow / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D016159:Tumor Suppressor Protein p53; D051879:Twist-Related Protein 1