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/EBPβ 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.

Iosue, I., Quaranta, R., Masciarelli, S., Fontemaggi, G., Batassa, E.m., Bertolami, C., et al. (2013). Argonaute 2 sustains the gene expression program driving human monocytic differentiation of acute myeloid leukemia cells. CELL DEATH & DISEASE, 4(11), e926 [10.1038/cddis.2013.452].

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

OTTONE, TIZIANA;LO COCO, FRANCESCO;
2013

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/EBPβ 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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - Malattie del Sangue
English
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; Receptors, Calcitriol
Iosue, I., Quaranta, R., Masciarelli, S., Fontemaggi, G., Batassa, E.m., Bertolami, C., et al. (2013). Argonaute 2 sustains the gene expression program driving human monocytic differentiation of acute myeloid leukemia cells. CELL DEATH & DISEASE, 4(11), e926 [10.1038/cddis.2013.452].
Iosue, I; Quaranta, R; Masciarelli, S; Fontemaggi, G; Batassa, E; Bertolami, C; Ottone, T; Divona, M; Salvatori, B; Padula, F; Fatica, A; LO COCO, F; Nervi, C; Fazi, F
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/160517
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