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Series GSE30656 Query DataSets for GSE30656
Status Public on Jun 28, 2012
Title Altered microRNA expression associated with chromosomal and epigenetic changes contributes to cervical carcinogenesis
Organism Homo sapiens
Experiment type Non-coding RNA profiling by array
Summary Little is known about the alterations in microRNA (miRNA) expression patterns during the consecutive stages of cervical cancer development and their association with chromosomal instability and epigenetic changes. We integrated miRNA expression profiles in normal cervical squamous epithelium, high-grade precancerous lesions (CIN2-3), squamous cell carcinomas (SCC) and adenocarcinomas (AdCAs) with previously generated chromosomal profiles of the same samples. In addition, the DNA methylation status of downregulated miRNAs located in a CpG island was determined. Significantly differential expression during the consecutive stages of cervical SCC development was observed for 106 miRNAs. Altered expression of 5 significantly differentially expressed miRNAs, hsa-miR-9 (1q23.2), hsa-miR-15b (3q25.32), hsa-miR-28-5p (3q27.3), hsa-miR-100 and hsa-miR-125b (both 11q24.1) was directly linked to frequent chromosomal alterations. Another 9 significantly downregulated miRNAs were located within a CpG island. Three of these 9 miRNAs, hsa-miR-203, hsa-miR-572, and hsa-miR-638, showed increased methylation in cervical cancer cell lines and HPV-immortalised cells compared to primary keratinocytes. Functional analyses were performed for hsa-miR-9, representing a potential oncogene with increased expression linked to a chromosomal gain, and hsa-miR-203, representing a potential tumour suppressor gene silenced by DNA methylation. Hsa-miR-9 and hsa-miR-203 were found to alter cell viability and anchorage independent growth in vitro, respectively, supporting their oncogenic and tumour suppressive function in cervical cancer. In conclusion, differential expression of 106 miRNAs, partly associated with chromosomal alterations and epigenetic changes, was observed during cervical SCC development. Altered expression of hsa-miR-9 and hsa-miR-203 was shown to be functionally relevant, underlining the importance of deregulated miRNA expression in cervical carcinogenesis.
Overall design 10 squamous cell carcinomas of the cervix, 9 adenocarcinomas of the cervix, 18 high-grade cervical intraepithelial neoplasias (CIN2-3), and 10 cervical squamous epithelial samples with normal histology were analysed using single channel (Cy3) miRNA microarrays from Agilent (G4471A-016436).
Contributor(s) Wilting SM, Snijders PJ, Verlaat W, Bosman-Jaspers A, vandeWiel MA, vanWieringen WN, Meijer GA, Kenter GG, Yi Y, leSage C, Agami R, Meijer CJ, Steenbergen RD
Citation(s) 22330141
Submission date Jul 14, 2011
Last update date Jun 30, 2012
Contact name Daoud Sie
Phone +31 20 4442428
Organization name Vrije Universiteit Medical Center
Department Pathology
Lab Microarray Core Facility
Street address De Boelelaan 1117
City Amsterdam
ZIP/Postal code 1081 HV
Country Netherlands
Platforms (1)
GPL6955 Agilent-016436 Human miRNA Microarray 1.0 (Feature Number version)
Samples (47)
GSM760507 Normal02218
GSM760508 Normal02371
GSM760509 Normal02449
BioProject PRJNA144605

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE30656_RAW.tar 32.4 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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