Identification Of Differently Expressed MicroRNA In Medulloblastoma And Function Analysis

Objective: MiRNAs are a group of highly conserved non-coding RNA and control hundreds of target genes by inhibiting translation, regulating mRNA splicing, promoting mRNA degradation and other measures. Therefore, they play an important role in tumor development. In recent years, there have been many studies about correlations between miRNAs and brain tumors. For the purpose of exploring the possible mechanism of miRNA regulation in medulloblastoma, the present study was designed to find out significantly differentially expressed miRNAs in medulloblastoma, and investigate their biological function by using bioinformatics tools to provide theoretical guidance and experimental envidence for future researchs about medulloblastoma pathogenesis.Method: Medulloblastoma cancer tissues and para-cancer tissues were collected, and Exiqon's miRNA chip miRCURYTM LNA Array (v13.0) were used to find out differentially expressed miRNAs. The significantly differentially expressed miRNA which had not been reported was testified by real-time quantitative PCR. TargetScanHuman online software was used to predict the potential target genes of this miRNA. GO Tree Machine software was used to explore GO annotation clustering of those target genes, then the function of those genes would be suggested from those enrichment of GO items. Finally, DAVID online platform was used to predict the enrichment of biological pathways of those genes.Results: Comparing with the control group, chips screened out that 21 miRNAs increased more than 2-fold, and 127 miRNAs decreased more than 2-fold in medulloblastoma. The real-time quantitative PCR validation results were consistent with the chip screening, which showed miR-130a significantly reduced. The result of TargetScanHuman 5.1 prediction showed that there were 265 potential target genes of miR-130a. Analysis of GO Tree Machine laid out that there were 36 target genes related to the development of the nervous system. The enriched pathways of target genes were predicted by DAVID, including MAPK signaling pathway, TGF-beta signaling pathway, Adherens junction and Wnt signaling pathway, all of which involved in the cancer pathway suggesting that miR-130a candidate target genes regulated biological process of cancer. It is worth noting that Ras/MAPK pathway which had been proved to be an important pathway in medulloblastoma by experiments was also included in our prediction results and the key gene in this pathway, PDGFRA, was the target of miR-130a as well.Conclusion: The miRNA expression profile of of medulloblastoma showed the down-regulated miRNAs were more than up-regulated ones. miR-130a was down-regulated very significantly. Bioinformatics analysis showed that miR-130a had hundreds of target genes, widely distributed in neural system development and tumorigenesis biological pathway, especially the Ras/MAPK pathway in medulloblastoma. Down-regulation of miR-130a induced the up-regulation of PDGFRA, the key gene in MAPK pathway, which might be the reason for up-regulation of Ras/MAPK signaling pathway in medulloblastoma.