Argonaute 2 drives miR-145-5p-dependent gene expression program in breast cancer cells

Silvia Masciarelli, Teresa Bellissimo, Claudia Tito, Federica Ganci, Andrea Sacconi, Giuseppe Di Martino, Natale Porta, Mirko Cirenza, Melissa Sorci, Luciana De Angelis, Paolo Rosa, Antonella Calogero, Alessandro Fatica, Vincenzo Petrozza, Giulia Fontemaggi, Giovanni Blandino, Francesco Fazi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

18 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)17-N/A
RivistaCELL DEATH & DISEASE
Volume10
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • A549 Cells
  • Argonaute Proteins
  • Breast Neoplasms
  • Cell Cycle
  • Cell Movement
  • Eukaryotic Initiation Factors
  • Female
  • Gene Expression
  • Humans
  • Kaplan-Meier Estimate
  • MCF-7 Cells
  • MicroRNAs
  • Polyribosomes
  • Protein Biosynthesis
  • Transfection

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