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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / analysis
  • Cell Line, Tumor
  • Cell Lineage
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Gain of Function Mutation
  • Gene Expression Regulation*
  • Granulocyte Precursor Cells / cytology
  • Granulocyte Precursor Cells / metabolism*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Kruppel-Like Factor 4
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology
  • Loss of Function Mutation
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Monocytes / cytology*
  • Myelopoiesis / physiology*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Peptide Nucleic Acids / pharmacology
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / physiology
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics

Substances

  • Antigens, CD34
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • MIRN130 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • Peptide Nucleic Acids
  • RNA, Neoplasm
  • Transcription Factors