miR-199a-5p inhibits monocyte/macrophage differentiation by targeting the activin A type 1B receptor gene and finally reducing C/EBPα expression.
J Leukoc Biol
; 96(6): 1023-35, 2014 Dec.
Article
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| MEDLINE
| ID: mdl-25258381
ABSTRACT
miRNAs are short, noncoding RNAs that regulate expression of target genes at post-transcriptional levels and function in many important cellular processes, including differentiation, proliferation, etc. In this study, we observed down-regulation of miR-199a-5p during monocyte/macrophage differentiation of HL-60 and THP-1 cells, as well as human CD34(+) HSPCs. This down-regulation of miR-199a-5p resulted from the up-regulation of PU.1 that was demonstrated to regulate transcription of the miR-199a-2 gene negatively. Overexpression of miR-199a-5p by miR-199a-5p mimic transfection or lentivirus-mediated gene transfer significantly inhibited monocyte/macrophage differentiation of the cell lines or HSPCs. The mRNA encoding an ACVR1B was identified as a direct target of miR-199a-5p. Gradually increased ACVR1B expression level was detected during monocyte/macrophage differentiation of the leukemic cell lines and HSPCs, and knockdown of ACVR1B resulted in inhibition of monocyte/macrophage differentiation of HL-60 and THP-1 cells, which suggested that ACVR1B functions as a positive regulator of monocyte/macrophage differentiation. We demonstrated that miR-199a-5p overexpression or ACVR1B knockdown promoted proliferation of THP-1 cells through increasing phosphorylation of Rb. We also demonstrated that the down-regulation of ACVR1B reduced p-Smad2/3, which resulted in decreased expression of C/EBPα, a key regulator of monocyte/macrophage differentiation, and finally, inhibited monocyte/macrophage differentiation.
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Base de datos:
MEDLINE
Asunto principal:
Monocitos
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Regulación del Desarrollo de la Expresión Génica
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Proteína alfa Potenciadora de Unión a CCAAT
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Receptores de Activinas Tipo I
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MicroARNs
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Hematopoyesis
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Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Leukoc Biol
Año:
2014
Tipo del documento:
Article