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Exp Cell Res. 2019 Sep 1;382(1):111445. doi: 10.1016/j.yexcr.2019.05.026. Epub 2019 May 29.

Physiological expression of miR-130a during differentiation of CD34+ human hematopoietic stem cells results in the inhibition of monocyte differentiation.

Author information

1
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl - IRCCS, Italy. Electronic address: fabiana.mammoli@irst.emr.it.
2
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125, Modena, Italy. Electronic address: sandra.parenti@unimore.it.
3
Sant'Orsola Malpighi Hospital, University of Bologna, Bologna, Italy. Electronic address: mariana.lomiento@aosp.bo.it.
4
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125, Modena, Italy. Electronic address: claudiogiacinto.atene@unimore.it.
5
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125, Modena, Italy. Electronic address: claudia.gemelli@unimore.it.
6
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125, Modena, Italy. Electronic address: alexis.grande@unimore.it.
7
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 17/A, I-43124 Parma, Italy. Electronic address: roberto.corradini@unipr.it.
8
Department of Organic and Macromolecular Chemistry Organic and Biomimetic Chemistry Research Group (OBCR) Faculty of Sciences - Ghent University Campus Sterre, Krijgslaan, 281 S4 B-9000 Gent, Belgium. Electronic address: alex.maardi@ugent.benic.
9
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125, Modena, Italy. Electronic address: sebastian.fantini@unimore.it.
10
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl - IRCCS, Italy. Electronic address: zanocco@unimore.it.
11
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125, Modena, Italy. Electronic address: sergio.ferrari@unimore.it.

Abstract

MicroRNAs (miRNA) are small noncoding RNAs that regulate gene expression by targeting mRNAs in a sequence specific manner, thereby determining their degradation or inhibiting translation. They are involved in processes such as proliferation, differentiation and apoptosis by fine-tuning the expression of genes underlying such events. The expression of specific miRNAs is involved in hematopoietic differentiation and their deregulation contributes to the development of hematopoietic malignancies such as acute myeloid leukemia (AML). miR-130a is over-expressed in AML. Here we show that miR-130a is physiologically expressed in myeloblasts and down-regulated during monocyte differentiation. Gain- and loss-of-function experiments performed on CD34+ human hematopoietic stem cells confirmed that expression of miR-130a inhibits monocyte differentiation by interfering with the expression of key transcription factors HOXA10, IRF8, KLF4, MAFB and PU-1. The data obtained in this study highlight that the correct modulation of miR-130a is necessary for normal differentiation to occur and confirming that deregulation of this miRNA might underlie the differentiation block occurring in AML.

KEYWORDS:

Acute myeloid leukemia; Differentiation; Hematopoiesis; Monocyte; Stem cell; Transcription factor; microRNA

PMID:
31152707
DOI:
10.1016/j.yexcr.2019.05.026
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