Affordable Access

deepdyve-link
Publisher Website

Loss of miR-107, miR-181c and miR-29a-3p Promote Activation of Notch2 Signaling in Pediatric High-Grade Gliomas (pHGGs).

Authors
  • Catanzaro, Giuseppina1
  • Sabato, Claudia2, 3
  • Russo, Michele4
  • Rosa, Alessandro5, 6
  • Abballe, Luana7
  • Besharat, Zein Mersini8
  • Po, Agnese9
  • Miele, Evelina10
  • Bellavia, Diana11
  • Chiacchiarini, Martina12, 13
  • Gessi, Marco14
  • Peruzzi, Giovanna15
  • Napolitano, Maddalena16
  • Antonelli, Manila17
  • Mastronuzzi, Angela18
  • Giangaspero, Felice19, 20
  • Locatelli, Franco21, 22
  • Screpanti, Isabella23, 24, 25
  • Vacca, Alessandra26
  • Ferretti, Elisabetta27, 28
  • 1 Department of Experimental Medicine, Sapienza University, Viale Regina Elena, 291, 00161 Rome, Italy. [email protected] , (Italy)
  • 2 Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy. [email protected] , (Italy)
  • 3 Center for Life [email protected], Istituto Italiano di Tecnologia, 00161 Rome, Italy. [email protected] , (Italy)
  • 4 Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy. [email protected] , (Italy)
  • 5 Center for Life [email protected], Istituto Italiano di Tecnologia, 00161 Rome, Italy. [email protected] , (Italy)
  • 6 Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy. [email protected] , (Italy)
  • 7 Department of Experimental Medicine, Sapienza University, Viale Regina Elena, 291, 00161 Rome, Italy. [email protected] , (Italy)
  • 8 Department of Experimental Medicine, Sapienza University, Viale Regina Elena, 291, 00161 Rome, Italy. [email protected] , (Italy)
  • 9 Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy. [email protected] , (Italy)
  • 10 Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy. [email protected] , (Italy)
  • 11 Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy. [email protected] , (Italy)
  • 12 Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy. [email protected] , (Italy)
  • 13 Center for Life [email protected], Istituto Italiano di Tecnologia, 00161 Rome, Italy. [email protected] , (Italy)
  • 14 Department of Histopathology, Fondazione Policlinico Universitario "A. Gemelli", Università Cattolica Sacro cuore, Largo A. Gemelli 8, 00168 Rome, Italy. [email protected] , (Italy)
  • 15 Center for Life [email protected], Istituto Italiano di Tecnologia, 00161 Rome, Italy. [email protected] , (Italy)
  • 16 Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy. [email protected] , (Italy)
  • 17 Department of Radiological, Oncological and Pathological Science, Sapienza University, 00161 Rome, Italy. [email protected] , (Italy)
  • 18 Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy. [email protected] , (Italy)
  • 19 Department of Radiological, Oncological and Pathological Science, Sapienza University, 00161 Rome, Italy. [email protected] , (Italy)
  • 20 Istituto di Ricovero e Cura a Carattere Scientifico Neuromed, Pozzilli, 86077 Isernia, Italy. [email protected] , (Italy)
  • 21 Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy. [email protected] , (Italy)
  • 22 Department of Pediatrics, University of Pavia, 27100 Pavia, Italy. [email protected] , (Italy)
  • 23 Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy. [email protected] , (Italy)
  • 24 Center for Life [email protected], Istituto Italiano di Tecnologia, 00161 Rome, Italy. [email protected] , (Italy)
  • 25 Institute Pasteur-Foundation Cenci Bolognetti, Sapienza University, 00161 Rome, Italy. [email protected] , (Italy)
  • 26 Department of Experimental Medicine, Sapienza University, Viale Regina Elena, 291, 00161 Rome, Italy. [email protected] , (Italy)
  • 27 Department of Experimental Medicine, Sapienza University, Viale Regina Elena, 291, 00161 Rome, Italy. [email protected] , (Italy)
  • 28 Istituto di Ricovero e Cura a Carattere Scientifico Neuromed, Pozzilli, 86077 Isernia, Italy. [email protected] , (Italy)
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
Dec 17, 2017
Volume
18
Issue
12
Identifiers
DOI: 10.3390/ijms18122742
PMID: 29258209
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The mechanisms by which microRNAs control pediatric high-grade gliomas (pHGGs) have yet to be fully elucidated. Our studies of patient-derived pHGG tissues and of the pHGG cell line KNS42 revealed down-regulation in these tumors of three microRNAs, specifically miR-107, miR-181c, and miR-29a-3p. This down-regulation increases the proliferation of KNS42 cells by de-repressing expression of the Notch2 receptor (Notch2), a validated target of miR-107 and miR-181c and a putative target of miR-29a-3p. Inhibition (either pharmacologic or genetic) of Notch2 or re-expression of the implicated microRNAs (all three combined but also individually) significantly reduced KNS42 cell proliferation. These findings suggest that Notch2 pathway activation plays a critical role in pHGGs growth and reveal a direct epigenetic mechanism that controls Notch2 expression, which could potentially be targeted by novel forms of therapy for these childhood tumors characterized by high-morbidity and high-mortality.

Report this publication

Statistics

Seen <100 times