High-throughput microRNA profile in adult and pediatric primary glioblastomas: the role of miR-10b-5p and miR-630 in the tumor aggressiveness

Autor: Luiz Gonzaga Tone, Luciana Chain Veronez, Ricardo Santos de Oliveira, Luciano Neder, Silvia Regina Brandalise, Simone dos Santos Aguiar, Carlos Gilberto Carlotti, Paola Fernanda Fedatto, Régia Caroline Peixoto Lira, Elvis Terci Valera, José Andrés Yunes, Carlos Alberto Scrideli, Vanessa da Silva Silveira, Luiz Guilherme Darrigo Junior, Hélio Rubens Machado, Veridiana K. Suazo, David S. Marco Antonio, Silvia A. Teixeira, Rodrigo Alexandre Panepucci, Mirella Baroni
Rok vydání: 2020
Předmět:
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 1573-4978
Popis: Glioblastoma (GBM) is the most common primary malignant neoplasm of the central nervous system and, despite the standard therapy; the patients’ prognoses remain dismal. The miRNA expression profiles have been associated with patient prognosis, suggesting that they may be helpful for tumor diagnosis and classification as well as predictive of tumor response to treatment. We described the microRNA expression profile of 29 primary GBM samples (9 pediatric GBMs) and 11 non-neoplastic white matter samples as controls (WM) by microarray analysis and we performed functional in vitro assays on these 2 most differentially expressed miRNAs. Hierarchical clustering analysis showed 3 distinct miRNA profiles, two of them in the GBM samples and a group consisting only of cerebral white matter. When adult and pediatric GBMs were compared to WM, 37 human miRNAs were found to be differentially expressed, with miR-10b-5p being the most overexpressed and miR-630 the most underexpressed. The overexpression of miR-630 was associated with reduced cell proliferation and invasion in the U87 GBM cell line, whereas the inhibition of miR-10b-5p reduced cell proliferation and colony formation in the U251 GBM cell line, suggesting that these miRNAs may act as tumor-suppressive and oncogenic miRNAs, respectively. The present study highlights the distinct epigenetic profiling of adult and pediatric GBMs and underscores the biological importance of mir-10b-5p and miR-630 for the pathobiology of these lethal tumors.
Databáze: OpenAIRE