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- Title
Loss of miR-107, miR-181c and miR-29a-3p Promote Activation of Notch2 Signaling in Pediatric High-Grade Gliomas (pHGGs).
- Authors
Catanzaro, Giuseppina; Sabato, Claudia; Russo, Michele; Rosa, Alessandro; Abballe, Luana; Besharat, Zein Mersini; Po, Agnese; Miele, Evelina; Bellavia, Diana; Chiacchiarini, Martina; Gessi, Marco; Peruzzi, Giovanna; Napolitano, Maddalena; Antonelli, Manila; Mastronuzzi, Angela; Giangaspero, Felice; Locatelli, Franco; Screpanti, Isabella; Vacca, Alessandra; Ferretti, Elisabetta
- 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.
- Subjects
MICRORNA; GLIOMAS; DOWNREGULATION; CELL proliferation; EPIGENETICS; TUMORS in children
- Publication
International Journal of Molecular Sciences, 2017, Vol 18, Issue 12, p2742
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms18122742