Argonaute 2 sustains the gene expression program driving human monocytic differentiation of acute myeloid leukemia cells

Silvia Masciarelli, I. Iosue, R. Quaranta, G. Fontemaggi, E. M. Batassa, C. Bertolami, T. Ottone, M. Divona, B. Salvatori, F. Padula, A. Fatica, F. Lo-Coco, C. Nervi, F. Fazi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

24 Citazioni (Scopus)

Abstract

MicroRNAs are key regulators of many biological processes, including cell differentiation. These small RNAs exert their function assembled in the RNA-induced silencing complexes (RISCs), where members of Argonaute (Ago) family of proteins provide a unique platform for target recognition and gene silencing. Here, by using myeloid cell lines and primary blasts, we show that Ago2 has a key role in human monocytic cell fate determination and in LPS-induced inflammatory response of 1,25-dihydroxyvitamin D3 (D3)-treated myeloid cells. The silencing of Ago2 impairs the D3-dependent miR-17-5p/20a/106a, miR-125b and miR-155 downregulation, the accumulation of their translational targets AML1, VDR and C/EBPb and monocytic cell differentiation. Moreover, we show that Ago2 is recruited on miR-155 host gene promoter and on the upstream region of an overlapping antisense lncRNA, determining their epigenetic silencing, and miR-155 downregulation. These findings highlight Ago2 as a new factor in myeloid cell fate determination in acute myeloid leukemia cells. © 2013 Macmillan Publishers Limited All rights reserved.
Lingua originaleEnglish
pagine (da-a)e926-e926
RivistaCELL DEATH & DISEASE
Volume4
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • Acute myeloid leukemia
  • Argonaute 2
  • Argonaute Proteins
  • Blotting, Western
  • CCAAT-Enhancer-Binding Proteins
  • Calcitriol
  • Cell Differentiation
  • Cell Line, Tumor
  • Core Binding Factor Alpha 2 Subunit
  • HL-60 Cells
  • Humans
  • Leukemia, Myeloid, Acute
  • MicroRNAs
  • Myeloid differentiation
  • Receptors, Calcitriol
  • microRNA

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