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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Darrigo Junior, Luiz Guilherme ^[1] ; Baroni, Mirella ^[2] ; Peixoto Lira, Regia Caroline ^{[3, 1]} ; Teixeira, Silvia ^[1] ; Fedatto, Paola Fernanda ^[1] ; Silveira, Vanessa Silva ^[2] ; Suazo, Veridiana Kill ^[1] ; Veronez, Luciana Chain ^[1] ; Panepucci, Rodrigo Alexandre ^[4] ; Marco Antonio, David Santos ^[5] ; Yunes, Jose Andres ^{[6, 7]} ; Brandalise, Silvia Regina ^[7] ; Aguiar, Simone dos Santos ^[6] ; Neder, Luciano ^[8] ; de Oliveira, Ricardo Santos ^[9] ; Machado, Helio Rubens ^[9] ; Carlotti Jr, Carlos Gilberto ; Tone, Luiz Gonzaga ^{[2, 1]} ; Valera, Elvis Terci ^[1] ; Scrideli, Carlos Alberto ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil

^[3] Ctr Univ CESMAC, Maceio, AL - Brazil

^[4] Univ Sao Paulo, Hemoctr Fdn, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

^[5] Fleury Grp, Dept Res & Dev, Sao Paulo, SP - Brazil

^[6] Univ Estadual Campinas, Campinas, SP - Brazil

^[7] Boldrinis Children Ctr, Campinas, SP - Brazil

^[8] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol, Ribeirao Preto, SP - Brazil

^[9] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg, Div Neurosurg, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR BIOLOGY REPORTS; v. 47, n. 9 SEP 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 10/07020-9 - Estudos moleculares em neoplasias da criança e do adolescente: assinatura de microRNAs e estudos funcionais de genes candidatos a terapia alvo
• Beneficiário: Carlos Alberto Scrideli
• Modalidade de apoio: Auxílio à Pesquisa - Regular