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Series GSE78277 Query DataSets for GSE78277
Status Public on Feb 09, 2017
Title Aberrant methylation-mediated silencing of microRNAs contributes to HPV-induced anchorage independence [methylation-Illumina]
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary Cervical cancer and a subset of anogenital and head-and-neck carcinomas are caused by persistent infection with high-risk types of the human papillomavirus (hrHPV). Early stages of hrHPV-induced carcinogenesis can be faithfully mimicked in vitro. A major hallmark of hrHPV-transformed cells is their ability to grow anchorage independently, an oncogenic trait known to depend on inactivation of tumour suppressor genes. This study used an in vitro model of hrHPV-induced transformation to delineate in a longitudinal manner to what extent DNA methylation-mediated silencing of tumour suppressive microRNAs (miRNAs) contributed to hrHPV-induced anchorage independence. Genome-wide miRNA expression profiles were yielded from anchorage dependent (n=11) and independent passages (n=19) of 4 hrHPV-immortalised keratinocyte cell lines with and without demethylating treatment (DAC). Unsupervised clustering analysis showed that overall miRNA expression patterns discriminated between anchorage dependent and independent cells. Ten miRNA genes potentially silenced by methylation were selected and validated by bisulfite sequencing and methylation-specific PCR. Hsa-mir-129-2, -137, -935, -3663, -3665, and -4281 showed increased methylation in both HPV-transformed keratinocytes and cervical cancer cell lines compared to primary keratinocytes. Mature miRNAs derived from hsa-mir-129-2, -137, -3663, and -3665 decreased anchorage independence in cervical cancer cell lines. Finally, significantly increased methylation of hsa-mir-129-2, -935, -3663, -3665, and -4281 was observed in cervical (pre)cancerous lesions, underlining the clinical relevance of our findings. In conclusion, methylation-mediated silencing of tumour suppressive miRNAs contributes to the acquisition of anchorage independence, supporting the importance of miRNAs during early stages of carcinogenesis and underlining their potential as both disease markers and therapeutic targets.
 
Overall design Anchorage independent passages of 4 independent HPV-transformed keratinocyte cell lines (FK16A and FK16B containing HPV16 and FK18A and FK18B containing HPV18) were analysed by Infinium HumanMethylation450 BeadChip. In addition, primary human foreskin keratinocytes of 2 donors without HPV were included as normal controls.
 
Contributor(s) Wilting SM, Miok V, Jaspers A, Boon D, Sørgård H, Lando M, Snoek BC, van Wieringen WN, Meijer CJ, Lyng H, Snijders PJ, Steenbergen RD
Citation(s) 27270309
Submission date Feb 24, 2016
Last update date Mar 22, 2019
Contact name Saskia Wilting
E-mail(s) s.wilting@vumc.nl
Organization name VU University Medical Center
Street address De Boelelaan 1117
City Amsterdam
ZIP/Postal code 1081 HV
Country Netherlands
 
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (6)
GSM2071074 EK074p5
GSM2071075 EK942RS
GSM2071076 FK16Ap220
This SubSeries is part of SuperSeries:
GSE78279 Aberrant methylation-mediated silencing of microRNAs contributes to HPV-induced anchorage independence
Relations
BioProject PRJNA313085

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
GSE78277_RAW.tar 232.0 Mb (http)(custom) TAR (of IDAT)
GSE78277_unmethylated_methylated_intensities.txt.gz 15.7 Mb (ftp)(http) TXT
Processed data included within Sample table

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