Vol. 123, No. 1 (Supplement) 2018
Supplement abstract

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

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  • Claudia Tito,
  • Teresa Bellissimo,
  • Federica Ganci,
  • Andrea Sacconi,
  • Silvia Masciarelli,
  • Natale Porta,
  • Mirko Cirenza,
  • Melissa Sorci,
  • Luciana De Angelis,
  • Alessandro Fatica,
  • Vincenzo Petrozza,
  • Giulia Fontemaggi,
  • Giovanni Blandino,
  • Francesco Fazi
Claudia Tito
Sapienza University of Rome, Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Rome
Teresa Bellissimo
Sapienza University of Rome, Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Rome
Federica Ganci
IRCCS - Regina Elena National Cancer Institute, Oncogenomic and Epigenetic Unit, Rome
Andrea Sacconi
IRCCS - Regina Elena National Cancer Institute, Oncogenomic and Epigenetic Unit, Rome
Silvia Masciarelli
Sapienza University of Rome, Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Rome
Natale Porta
Sapienza University of Rome, Department of Medico-Surgical Sciences and Biotechnologies, Pathology Unit, ICOT, Latina
Mirko Cirenza
Sapienza University of Rome, Department of Medico-Surgical Sciences and Biotechnologies, Pathology Unit, ICOT, Latina
Melissa Sorci
Sapienza University of Rome, Department of Biology and Biotechnology “C. Darwin”, Rome
Luciana De Angelis
Sapienza University of Rome, Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Rome
Alessandro Fatica
Sapienza University of Rome, Department of Biology and Biotechnology “C. Darwin”, Rome
Vincenzo Petrozza
Sapienza University of Rome, Department of Medico-Surgical Sciences and Biotechnologies, Pathology Unit, ICOT, Latina
Giulia Fontemaggi
IRCCS - Regina Elena National Cancer Institute, Oncogenomic and Epigenetic Unit, Rome
Giovanni Blandino
IRCCS - Regina Elena National Cancer Institute, Oncogenomic and Epigenetic Unit, Rome
Francesco Fazi
Sapienza University of Rome, Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Rome
DOI: https://doi.org/10.13128/ijae-11542

Published 2018-12-30

Keywords

  • microRNAs,
  • miR-145-5p,
  • Ago2,
  • breast cancer,
  • cell migration

How to Cite

Tito, C., Bellissimo, T., Ganci, F., Sacconi, A., Masciarelli, S., Porta, N., Cirenza, M., Sorci, M., De Angelis, L., Fatica, A., Petrozza, V., Fontemaggi, G., Blandino, G., & Fazi, F. (2018). Argonaute 2 drives miR-145-dependent gene expression program influencing epithelial to mesenchymal transition in breast cancer cells. Italian Journal of Anatomy and Embryology, 123(1), 216. https://doi.org/10.13128/ijae-11542
Copyright Notice

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) [1]. While the mature miRNA guides the RISC complex to its target mRNA, the Ago protein represses mRNA translation [2]. 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 can- cer (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 induc- tion 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 performs Ago2-dependent and -independent activities. Our results highlight that the Ago2 protein in cancer cells strictly dictates miR-145-5p tumor suppressor activity.

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