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

Luiz Guilherme Darrigo Junior, Mirella Baroni, Régia Caroline Peixoto Lira, Silvia Teixeira, Paola Fernanda Fedatto, Vanessa Silva Silveira, Veridiana Kill Suazo, Luciana Chain Veronez, Rodrigo Alexandre Panepucci, David Santos Marco Antônio, José Andres Yunes, Silvia Regina Brandalise, Simone dos Santos Aguiar, Luciano Neder, Ricardo Santos de Oliveira, Hélio Rubens Machado, Carlos Gilberto Carlotti, Luiz Gonzaga Tone, Elvis Terci Valera, Carlos Alberto Scrideli*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6949-6959
Number of pages11
JournalMolecular Biology Reports
Volume47
Issue number9
DOIs
Publication statusPublished - 1 Sept 2020
Externally publishedYes

Keywords

  • Glioblastoma
  • miR-10b
  • miR-630
  • miRNA

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