title: 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.
authors.affiliation: 1] Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina 04100, Italy [2] San Raffaele Bio-Medical Park Foundation, Rome 00128, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Iosue
authors.forename: R
authors.initials: R
authors.lastname: Quaranta
authors.forename: S
authors.initials: S
authors.lastname: Masciarelli
authors.forename: G
authors.initials: G
authors.lastname: Fontemaggi
authors.forename: E M
authors.initials: EM
authors.lastname: Batassa
authors.forename: C
authors.initials: C
authors.lastname: Bertolami
authors.forename: T
authors.initials: T
authors.lastname: Ottone
authors.forename: M
authors.initials: M
authors.lastname: Divona
authors.forename: B
authors.initials: B
authors.lastname: Salvatori
authors.forename: F
authors.initials: F
authors.lastname: Padula
authors.forename: A
authors.initials: A
authors.lastname: Fatica
authors.forename: F
authors.initials: F
authors.lastname: Lo-Coco
authors.forename: C
authors.initials: C
authors.lastname: Nervi
authors.forename: F
authors.initials: F
authors.lastname: Fazi
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism
chemical_list: D060565:Argonaute Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D050676:Core Binding Factor Alpha 2 Subunit; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C493728:RUNX1 protein, human; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D002117:Calcitriol