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Series GSE138079 Query DataSets for GSE138079
Status Public on Apr 06, 2020
Title Identification of deregulated pathways, key regulators, and novel miRNA-mRNA interactions in HPV-mediated transformation. [mRNA cell lines-Agilent]
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Next to a persistent infection with high-risk human papillomavirus (HPV), molecular changes are required for the development of cervical cancer. To identify which molecular alterations drive carcinogenesis, we performed a comprehensive and longitudinal molecular characterization of HPV-transformed keratinocyte cell lines. Comparative genomic hybridization, mRNA, and miRNA expression analysis of four HPV-containing keratinocyte cell lines at eight different time points was performed. Data was analyzed using unsupervised hierarchical clustering, integrated longitudinal expression analysis, and pathway enrichment analysis. Biological relevance of identified key regulatory genes was evaluated in vitro and dual-luciferase assays were used to confirm predicted miRNA-mRNA interactions. We show that the acquisition of anchorage independence of HPV-containing keratinocyte cell lines is particularly associated with copy number alterations. Approximately one third of differentially expressed mRNAs and miRNAs was directly attributable to copy number alterations. Focal adhesion, TGF-beta signaling, and mTOR signaling pathways were enriched among these genes. PITX2 was identified as key regulator of TGF-beta signaling and inhibited cell growth in vitro, most likely by inducing cell cycle arrest and apoptosis. Predicted miRNA-mRNA interactions miR-221-3p_BRWD3, miR-221-3p_FOS, and miR-138-5p_PLXNB2 were confirmed in vitro. Integrated longitudinal analysis of our HPV-induced carcinogenesis model pinpointed relevant interconnected molecular changes and crucial signaling pathways in HPV-mediated transformation.
 
Overall design Expression profiles of 8 sequential passages of 4 HPV-transformed human foreskin primary keratinocyte cell lines either treated with or without demethylation agent DAC were analyzed using whole human genome oligo microarrays (G4112A, mRNA 4x44K; Agilent).
Web link https://www.ncbi.nlm.nih.gov/pubmed/32188026
 
Contributor(s) Babion I, Miok V, Jaspers A, Huseinovic A, Steenbergen RD, vanWieringen WN, Wilting SM
Citation(s) 32188026
Submission date Sep 26, 2019
Last update date Apr 08, 2020
Contact name Renske DM Steenbergen
E-mail(s) r.steenbergen@amsterdamumc.nl
Organization name Amsterdam UMC, location VUmc
Department Pathology
Lab Molecular Pathology
Street address De Boelelaan 1117
City Amsterdam
ZIP/Postal code 1081 HV
Country Netherlands
 
Platforms (1)
GPL4133 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
Samples (64)
GSM4098797 HPV16-transfected human foreskin keratinocytes_line A_timepoint 1_untreated
GSM4098798 HPV16-transfected human foreskin keratinocytes_line A_timepoint 2_untreated
GSM4098799 HPV16-transfected human foreskin keratinocytes_line A_timepoint 3_untreated
This SubSeries is part of SuperSeries:
GSE138081 Identification of deregulated pathways, key regulators, and novel miRNA-mRNA interactions in HPV-mediated transformation.
Relations
BioProject PRJNA574466

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
GSE138079_Agilent_Feature_Extraction_files_1.tar.gz 488.9 Mb (ftp)(http) TAR
GSE138079_RAW.tar 6.9 Mb (http)(custom) TAR
Processed data included within Sample table
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