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

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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

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

doi

10.1038/cddis.2013.452

subject

Has Abstract

pub_date

2013-11-21 00:00:00

pages

e926

issn

2041-4889

pii

cddis2013452

journal_volume

4

pub_type

杂志文章

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