Dataset Information

A catalogue of glioblastoma and brain MicroRNAs identified by deep sequencing.

ABSTRACT: Glioblastoma is the most common and aggressive primary brain tumor. MicroRNAs (miRNAs) are a set of noncoding RNA of about 20?22?nt in length and they play regulatory roles such as regulating the expression of proteins. Altered miRNA expression is related to cancers, including glioblastoma. In this report, we used deep sequencing to explore the miRNA profiles of glioblastoma and normal brain tissues. We found 875 and 811 known miRNA and miRNA* in glioblastoma and normal brain tissue, respectively, representing the largest characterization of the miRNAs in GBM so far. 33 of them were upregulated in glioblastoma, including miR-21, which is well known as an oncomir, while 40 of them were downregulated. Using miR-10b, miR-124, miR-433, and miR-92b as examples, we verified the data by quantitative RT-PCR, suggesting that deep sequencing was able to capture the expression profiles of miRNAs. In addition, we found 18 novel miRNA and 16 new miRNA* in glioblastoma and normal brain tissues. This report provides a useful resource for future studies of the roles of miRNAs in the pathogenesis and early detection of glioblastoma.

SUBMITTER: Hua D

PROVIDER: S-EPMC3521142 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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A catalogue of glioblastoma and brain MicroRNAs identified by deep sequencing.

Hua Dasong D Mo Fan F Ding Dong D Li Lisa L Han Xu X Zhao Na N Foltz Gregory G Lin Biaoyang B Lan Qing Q Huang Qiang Q

Omics : a journal of integrative biology 20121201 12

Glioblastoma is the most common and aggressive primary brain tumor. MicroRNAs (miRNAs) are a set of noncoding RNA of about 20∼22 nt in length and they play regulatory roles such as regulating the expression of proteins. Altered miRNA expression is related to cancers, including glioblastoma. In this report, we used deep sequencing to explore the miRNA profiles of glioblastoma and normal brain tissues. We found 875 and 811 known miRNA and miRNA* in glioblastoma and normal brain tissue, respectivel ...[more]

PMID: 23215807

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Project description:BackgroundHypoxia is a critical aspect of the glioma microenvironment and has been associated with poor prognosis and resistance to various therapies. However, the mechanisms responsible for hypoxic survival of glioma cells remain unclear. Recent studies strongly suggest that microRNAs act as critical mediators of the hypoxic response. We thus hypothesized their prominent role in hypoxia resistance in glioblastoma (GBM) and aimed to identify those.ResultsWith this study, we present the first detailed analysis of small RNA transcriptome of cell line U87MG, a grade IV glioma cell line, and its alteration under hypoxic condition. Based on deep sequencing and microarray data, we identify a set of hypoxia regulated microRNAs, with the miR-210-3p and its isomiRs showing highest induction in GBM cell lines U87MG and U251MG. We show miR-210-3p, miR-1275, miR-376c-3p, miR-23b-3p, miR-193a-3p and miR-145-5p to be up-regulated, while miR-92b-3p, miR-20a-5p, miR-10b-5p, miR-181a-2-3p and miR-185-5p are down-regulated by hypoxia. Interestingly, certain hypoxia-induced miRNAs are also known to be over-expressed in GBM tumors, suggesting that hypoxia may be one of the factors involved in establishing the miRNA signature of GBM. Transcription factor binding sites for Hypoxia inducible factor 1 A (HIF1A) were identified in the promoter region (5 kb upstream) of 30 hypoxia-induced miRNAs. HIF-1A over-expression and silencing studies show regulation of specific miRNAs, including miR-210-3p, to be HIF1A dependent. On the other hand, miR-210-3p leads to an increase in transcriptional activity of HIF and its target genes vascular endothelial growth factor (VEGF) and carbonic anhydrase 9 (CA9). MiR-210-3p levels were found to be high in GBM patient samples and showed good correlation with the known hypoxia markers CA9 and VEGF. We show that miR-210-3p promotes hypoxic survival and chemoresistance in GBM cells and targets a negative regulator of hypoxic response, HIF3A. Additionally, a total of 139 novel miRNAs were discovered by the analysis of deep sequencing data and three of these were found to be differentially expressed under hypoxia.ConclusionsOverall, our study reveals a novel miRNA signature of hypoxia in GBM and suggests miR-210-3p to be an oncogenic player and a novel potential intrinsic marker of hypoxia in glioblastoma.

Dataset Information

A catalogue of glioblastoma and brain MicroRNAs identified by deep sequencing.

Publications

A catalogue of glioblastoma and brain MicroRNAs identified by deep sequencing.

Similar Datasets

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