To perform their regulatory functions, microRNAs (miRNAs) must assemble with any of the four mammalian Argonaute (Ago) family of proteins, Ago1–4, into an effector complex known as the RNA-induced silencing complex (RISC). While the mature miRNA guides the RISC complex to its target mRNA, the Ago protein represses mRNA translation. The specific roles of the various Ago members in mediating miRNAs activity, however, haven’t been clearly established. In this study, we investigated the contribution of Ago2, the only human Ago protein endowed with nuclease activity, to the function of tumor-suppressor miR-145-5p in breast cancer (BC). We show that miR-145-5p and Ago2 protein are concomitantly downregulated in BC tissues and that restoration of miR-145-5p expression in BC cells leads to Ago2 protein induction through the loosening of Ago2 mRNA translational repression. Functionally, miR-145-5p exerts its inhibitory activity on cell migration only in presence of Ago2, while, upon Ago2 depletion, we observed increased miR-145/Ago1 complex and enhanced cell motility. Profiling by microarray of miR-145-5p target mRNAs, in BC cells depleted or not of Ago2, revealed that miR-145-5p drives Ago2-dependent and –independent activities. Our results highlight that the Ago2 protein in cancer cells strictly dictates miR-145-5p tumor suppressor activity.

Argonaute 2 drives miR-145-dependent gene expression program influencing epithelial to mesenchymal transition in breast cancer cells / Tito, Claudia; Bellissimo, Teresa; Ganci, Federica; Sacconi, Andrea; Masciarelli, Slvia; Porta, Natale; Cirenza, Mirko; Sorci, Melissa; DE ANGELIS, Luciana; Fatica, Alessandro; Petrozza, Vincenzo; Fontemaggi, Giulia; Blandino, Giovanni; Fazi, Francesco. - In: ITALIAN JOURNAL OF ANATOMY AND EMBRYOLOGY. - ISSN 1122-6714. - STAMPA. - 123:n.1 (Supplement)(2018), pp. 216-216. (Intervento presentato al convegno 72° Congresso della Società di Anatomia e istologia tenutosi a Parma).

Argonaute 2 drives miR-145-dependent gene expression program influencing epithelial to mesenchymal transition in breast cancer cells

Claudia Tito;Teresa Bellissimo;Natale Porta;Melissa Sorci;Luciana De Angelis;Alessandro Fatica;Vincenzo Petrozza;Francesco Fazi
2018

Abstract

To perform their regulatory functions, microRNAs (miRNAs) must assemble with any of the four mammalian Argonaute (Ago) family of proteins, Ago1–4, into an effector complex known as the RNA-induced silencing complex (RISC). While the mature miRNA guides the RISC complex to its target mRNA, the Ago protein represses mRNA translation. The specific roles of the various Ago members in mediating miRNAs activity, however, haven’t been clearly established. In this study, we investigated the contribution of Ago2, the only human Ago protein endowed with nuclease activity, to the function of tumor-suppressor miR-145-5p in breast cancer (BC). We show that miR-145-5p and Ago2 protein are concomitantly downregulated in BC tissues and that restoration of miR-145-5p expression in BC cells leads to Ago2 protein induction through the loosening of Ago2 mRNA translational repression. Functionally, miR-145-5p exerts its inhibitory activity on cell migration only in presence of Ago2, while, upon Ago2 depletion, we observed increased miR-145/Ago1 complex and enhanced cell motility. Profiling by microarray of miR-145-5p target mRNAs, in BC cells depleted or not of Ago2, revealed that miR-145-5p drives Ago2-dependent and –independent activities. Our results highlight that the Ago2 protein in cancer cells strictly dictates miR-145-5p tumor suppressor activity.
2018
72° Congresso della Società di Anatomia e istologia
04 Pubblicazione in atti di convegno::04d Abstract in atti di convegno
Argonaute 2 drives miR-145-dependent gene expression program influencing epithelial to mesenchymal transition in breast cancer cells / Tito, Claudia; Bellissimo, Teresa; Ganci, Federica; Sacconi, Andrea; Masciarelli, Slvia; Porta, Natale; Cirenza, Mirko; Sorci, Melissa; DE ANGELIS, Luciana; Fatica, Alessandro; Petrozza, Vincenzo; Fontemaggi, Giulia; Blandino, Giovanni; Fazi, Francesco. - In: ITALIAN JOURNAL OF ANATOMY AND EMBRYOLOGY. - ISSN 1122-6714. - STAMPA. - 123:n.1 (Supplement)(2018), pp. 216-216. (Intervento presentato al convegno 72° Congresso della Società di Anatomia e istologia tenutosi a Parma).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1156887
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