TY - JOUR
T1 - Loss of miR-107, miR-181c and miR-29a-3p promote activation of Notch2 signaling in pediatric high-grade gliomas (pHGGs)
AU - Catanzaro, Giuseppina
AU - Sabato, Claudia
AU - Russo, Michele
AU - Rosa, Alessandro
AU - Abballe, Luana
AU - Besharat, Zein Mersini
AU - Po, Agnese
AU - Miele, Evelina
AU - Bellavia, Diana
AU - Chiacchiarini, Martina
AU - Gessi, Marco
AU - Peruzzi, Giovanna
AU - Napolitano, Maddalena
AU - Antonelli, Manila
AU - Mastronuzzi, Angela
AU - Giangaspero, Felice
AU - Locatelli, Franco
AU - Screpanti, Isabella
AU - Vacca, Alessandra
AU - Ferretti, Elisabetta
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Cell proliferation
KW - MiR-107
KW - MiR-181c
KW - MiR-29a-3p
KW - MicroRNAs
KW - Notch2 signaling
KW - Pediatric high-grade gliomas
KW - Cell proliferation
KW - MiR-107
KW - MiR-181c
KW - MiR-29a-3p
KW - MicroRNAs
KW - Notch2 signaling
KW - Pediatric high-grade gliomas
UR - http://hdl.handle.net/10807/229635
U2 - 10.3390/ijms18122742
DO - 10.3390/ijms18122742
M3 - Article
SN - 1661-6596
VL - 18
SP - 1
EP - 12
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
ER -