Unknown,Transcriptomics,Genomics,Proteomics

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Malignant Germ Cell Tumors Display Common microRNA Profiles Resulting in Global Changes in Expression of mRNA Targets

ABSTRACT: Comparison of miRNA expression profiles in malignant germ cell tumors compared to non-malignant control group. Use of bioinformatic algorithm Sylamer to interrogate mRNA expression profiles from malignant germ cell tumors for enrichment or depletion of binding sites for differentially expressed miRNAs. Use of Gene Ontology (GO) analysis to demonstrate functional significance of differentially expressed miRNAs in malignant germ cell tumors. mRNA profiling: Analyzed global mRNA expresion profiles from 21 pediatric samples (17 malignant germ cell tumors, 1 benign germ cell tumor and 3 gonadal controls) using Sylamer (van Dongen et al, Nature Methods 2008, PMID 18978784) to study functional significance of differentially expressed miRNAs in malignant germ cell tumors. 16 of these files previously published - Palmer et al, Cancer Research 2008, PMID 18519683; GEO Accession Number GSE10615. Similarly, re-analyzed published global mRNA expresion profiles from 25 adult samples (20 malignant germ cell tumors and 5 testis controls) using Sylamer (van Dongen et al, Nature Methods 2008, PMID 18978784) to study functional significance of differentially expressed miRNAs in malignant germ cell tumors. These files previously published - Korkola at al, Cancer Research 2006, PMID 16424014; GEO Accession Number GSE3218. miRNA profiling: Analyzed global miRNA expression files from 48 samples including 32 pediatric gonadal and extragonadal germ cell tumors, 2 adult testicular seminomas, 8 gonadal and developmental control samples and 6 germ cell tumor cell lines. Re-analyzed published data (TaqMan MicroRNA Assays) from study of miRNA expression in adult gonadal germ cell tumors (Gillis et al, J Pathol 2007, PMID 17893849) and compared with pediatric findings. Re-analyzed data linked below as supplementary file.

ORGANISM(S): Homo sapiens

SUBMITTER: Matthew Murray

PROVIDER: E-GEOD-18155 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Although gain of chromosome-5p is one of the most frequent DNA copy number imbalances in cervical squamous cell carcinoma (SCC), the genes that drive its selection remain poorly understood. In a previous cross-sectional clinical study we showed that the microRNA processor Drosha (located on chromosome-5p) demonstrates frequent copy-number gain and over-expression in cervical SCC, associated with altered microRNA profiles. Here, we have conducted gene depletion/over-expression experiments to demonstrate the functional significance of up-regulated Drosha in cervical SCC cells. Drosha depletion by RNA-interference (RNAi) produced significant, specific reductions in cell motility/invasiveness in vitro, with a silent RNAi-resistant Drosha mutation providing phenotype rescue. Unsupervised hierarchical clustering following global profiling of 319 microRNAs in eighteen cervical SCC cell line specimens generated two groups according to Drosha expression levels. Altering Drosha levels in individual SCC lines changed the group into which the cells clustered, with gene depletion effects being rescued by the RNAi-resistant mutation. Forty-five microRNAs showed significant differential expression between the groups, including four of fourteen that were differentially-expressed in association with Drosha levels in clinical samples. miR-31 up-regulation in Drosha over-expressing samples/cell lines was the highest-ranked change (by adjusted p-value) in both analyses, an observation validated by Northern blotting. These functional data support the role of Drosha as an oncogene in cervical SCC, by affecting expression of cancer-associated microRNAs that have the potential to regulate numerous protein-coding genes. This SuperSeries is composed of the following subset Series: GSE26175: Functional evidence that Drosha over-expression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles [miRNA] GSE26176: Functional evidence that Drosha over-expression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles [mRNA] Refer to individual Series

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Malignant Germ Cell Tumors Display Common microRNA Profiles Resulting in Global Changes in Expression of mRNA Targets

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