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 JuniorMirella BaroniRégia Caroline Peixoto LiraSilvia TeixeiraPaola Fernanda FedattoVanessa Silva SilveiraVeridiana Kill SuazoLuciana Chain VeronezRodrigo Alexandre PanepucciDavid Santos Marco AntônioJosé Andres YunesSilvia Regina BrandaliseSimone Dos Santos AguiarLuciano NederRicardo Santos de OliveiraHélio Rubens MachadoCarlos Gilberto CarlottiLuiz Gonzaga ToneElvis Terci ValeraCarlos Alberto ScrideliPublished in: Molecular biology reports (2020)
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.
Keyphrases
- cell proliferation
- white matter
- long non coding rna
- high throughput
- single cell
- long noncoding rna
- cell cycle
- childhood cancer
- end stage renal disease
- pi k akt
- gene expression
- stem cells
- multiple sclerosis
- machine learning
- endothelial cells
- newly diagnosed
- dna methylation
- prognostic factors
- chronic kidney disease
- deep learning
- case report
- bone marrow
- mesenchymal stem cells
- peritoneal dialysis
- signaling pathway
- combination therapy
- young adults
- patient reported