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Series GSE26177 Query DataSets for GSE26177
Status Public on May 26, 2011
Title Functional evidence that Drosha over-expression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles
Platform organisms Homo sapiens; Human alphaherpesvirus 1; Human alphaherpesvirus 2; Human betaherpesvirus 5; Lymphocryptovirus; Rhadinovirus; JC polyomavirus; Human immunodeficiency virus 1; Merkel cell polyomavirus; Betapolyomavirus hominis; Betapolyomavirus macacae
Sample organism Homo sapiens
Experiment type Non-coding RNA profiling by array
Expression profiling by array
Summary 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 SubSeries listed below.
 
Overall design Refer to individual Series.
 
Citation(s) 21590768
Submission date Dec 20, 2010
Last update date Mar 25, 2019
Contact name Matthew Jonathan Murray
E-mail(s) mjm16@cam.ac.uk
Phone 07976413769
Organization name MRC Cancer Cell Unit
Department MRC/Hutchison Research Centre
Lab 2.5
Street address Box 197, Hills Road
City Cambridge
ZIP/Postal code CB2 0XZ
Country United Kingdom
 
Platforms (2)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GPL11338 Exiqon miRCURY LNA microRNA Array, v.8.0 - all organisms (miRBase 14.0)
Samples (24)
GSM642814 Malignant cervical carcinoma cell line; manipulated_CaSki.dup2kd
GSM642815 Malignant cervical carcinoma cell line; manipulated_CaSki.dup3kd
GSM642816 Malignant cervical carcinoma cell line; manipulated_MS751.v
This SuperSeries is composed of the following SubSeries:
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]
Relations
BioProject PRJNA135259

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE26177_RAW.tar 38.7 Mb (http)(custom) TAR (of CEL, TXT)

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