MICRORNAS PROFILE IN PAEDIATRIC GBMS

Giunti, Laura;Da Ros, Martina;Iorio, Anna Lisa;Magi, Alberto;Mazzinghi, Benedetta;Giglio, Sabrina

Conceptualization

;Sardi, Iacopo

2017-01-01

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Abstract

MicroRNAs are a novel class of gene regulators and are involved in several physiologic cellular mechanisms, anti-viral defense, cancer and drug sensitivity/resistance of several tumors. Recently, specific microRNA expression profiles have been identified in Glioblastoma Multiforme (GBM), but there are only limited data on the role of microRNA in pediatric GBM (pGBM). In this study we explored the expression profile of 377 microRNAs in 3 pGBM versus a pool of 5 no-tumor pediatric cerebral cortex using TaqMan® Human MicroRNA Array v2.0, Applied Biosystems. We identified a set of microRNAs differentially expressed: miR-490, miR-876-3p and miR-876-5p, miR-448 (under expressed) and miR-501-3p (overexpressed). Through Bioinformatic analysis of this set of miRNAs, we predicted a series of hypothetical target genes: GRIA1, SORL1, NUCKS1, SOX11, SAP30L, HTT, PXMP4, THRB, PSD3, SPN, AGPAT4, USP31, GRIK3, POM121L8P, TNRC6B, SNX29, HIPK2, RIMKLA, ZNF738, LOC388692. We individually validated the expression of all of these genes in 3 pGBM and in 3 cell lines of human GBM (U87MG, A172 and T98G). Interestingly, drug resistant T98G cell line showed an over expression of NUCKS1 (nuclear, casein kinase and cyclin-dependent kinase substrate 1), a cell cycle-related protein that plays an important role in cell proliferation and cell progression. NUCKS1 is overexpressed in many tumors but its precise role in cancer development remains unknown. On the basis of this preliminary report it could be of paramount importance to investigate the role of miR-501-3p and NUCKS1 in the multidrug resistance mechanism of pediatric brain tumors.