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

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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.

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Funding

This study was supported by the Brazilian Public Research Agencies: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Grant Number: 2010/07020-9) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Grant Number: 471885/2013-4).

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Authors and Affiliations

  1. Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo – USP, Avenida dos Bandeirantes, 3900, Ribeirao Preto, 14049-900, Brazil

    Luiz Guilherme Darrigo Junior, Régia Caroline Peixoto Lira, Silvia Teixeira, Paola Fernanda Fedatto, Veridiana Kill Suazo, Luciana Chain Veronez, Luiz Gonzaga Tone, Elvis Terci Valera & Carlos Alberto Scrideli

  2. Department of Genetics, Ribeirão Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil

    Mirella Baroni, Vanessa Silva Silveira & Luiz Gonzaga Tone

  3. Centro Universitário CESMAC, Maceió, AL, Brazil

    Régia Caroline Peixoto Lira

  4. Hemocentro Foundation, Ribeirão Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil

    Rodrigo Alexandre Panepucci

  5. Department of Research and Development, Fleury Group, São Paulo, SP, Brazil

    David Santos Marco Antônio

  6. Boldrini’s Children Center, Campinas, SP, Brazil

    José Andres Yunes & Silvia Regina Brandalise

  7. State University of Campinas, Campinas, SP, Brazil

    José Andres Yunes & Simone dos Santos Aguiar

  8. Department of Pathology, Ribeirão Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil

    Luciano Neder

  9. Division of Neurosurgery, Department of Surgery, Ribeirão Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil

    Ricardo Santos de Oliveira, Hélio Rubens Machado & Carlos Gilberto Carlotti Jr

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  1. Luiz Guilherme Darrigo Junior
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Contributions

LGDJ, MB, LGT and CAS designed the project; LGDJ, MB, RCPL, ST, PFF, VSS, VKS, LCV, RAP and DSMA conducted the experiments and microarray analysis; LGDJ, MB, MB, JAY, SRB, SSA, LN, RSO, HRM, CGC, LGT, ETV, CAS were responsible for acquisition, analysis, or interpretation of data; LGDJ, MB, ETV and CAS wrote the manuscript. All authors revised and approved the final version.

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Correspondence to Carlos Alberto Scrideli.

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Junior, L.G.D., Baroni, M., Lira, R.C.P. et al. High-throughput microRNA profile in adult and pediatric primary glioblastomas: the role of miR-10b-5p and miR-630 in the tumor aggressiveness. Mol Biol Rep 47, 6949–6959 (2020). https://doi.org/10.1007/s11033-020-05754-3

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