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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/EBP? 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.

SUBMITTER: Iosue I 

PROVIDER: S-EPMC3847328 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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

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

Cell death & disease 20131121


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-dihydroxyvita  ...[more]

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