Virus Dataset Detail

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Dataset Information
Accession GSE138080
Status 2020/4/6
Title Identification of deregulated pathways, key regulators, and novel miRNA-mRNA interactions in HPV-mediated transformation
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.
Samples
GSM ID Sample info Characteristics Description
GSM4098861 Normal01194 cell type:normal cervical squamous epithelium; hpv:high-risk HPV-positive raw data file: US22502676_251485063644_S01_GE2-v5_95_Feb07_1_4.txt;none;VUMC_Normal01194
GSM4098862 Normal01265 cell type:normal cervical squamous epithelium; hpv:high-risk HPV-positive raw data file: US22502676_251485063642_S01_GE2-v5_95_Feb07_1_1.txt;none;VUMC_Normal01265
GSM4098863 Normal01306 cell type:normal cervical squamous epithelium; hpv:high-risk HPV-positive raw data file: US22502676_251485063643_S01_GE2-v5_95_Feb07_1_3.txt;none;VUMC_Normal01306
GSM4098864 Normal0196 cell type:normal cervical squamous epithelium; hpv:high-risk HPV-positive raw data file: US22502676_251485063643_S01_GE2-v5_95_Feb07_1_2.txt;none;VUMC_Normal0196
GSM4098865 Normal02218 cell type:normal cervical squamous epithelium; hpv:high-risk HPV-positive raw data file: US22502676_251485063646_S01_GE2-v5_95_Feb07_1_1.txt;none;VUMC_Normal02218
GSM4098866 Normal02371 cell type:normal cervical squamous epithelium; hpv:high-risk HPV-positive raw data file: US22502676_251485063646_S01_GE2-v5_95_Feb07_1_3.txt;none;VUMC_Normal02371
GSM4098867 Normal02400 cell type:normal cervical squamous epithelium; hpv:high-risk HPV-positive raw data file: US22502676_251485063644_S01_GE2-v5_95_Feb07_1_1.txt;none;VUMC_Normal02400
GSM4098868 Normal02449 cell type:normal cervical squamous epithelium; hpv:HPV-negative raw data file: US22502676_251485063642_S01_GE2-v5_95_Feb07_1_4.txt;none;VUMC_Normal02449
GSM4098869 Normal03764 cell type:normal cervical squamous epithelium; hpv:high-risk HPV-positive raw data file: US22502676_251485063645_S01_GE2-v5_95_Feb07_1_2.txt;none;VUMC_Normal03764
GSM4098870 Normal04441 cell type:normal cervical squamous epithelium; hpv:high-risk HPV-positive raw data file: US22502676_251485063645_S01_GE2-v5_95_Feb07_1_3.txt;none;VUMC_Normal04441
GSM4098871 HGCIN4 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063643_S01_GE2-v5_95_Feb07_1_4.txt;none;VUMC_HGCIN4
GSM4098872 HGCIN5 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063646_S01_GE2-v5_95_Feb07_1_2.txt;none;VUMC_HGCIN5
GSM4098873 HGCIN7 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063643_S01_GE2-v5_95_Feb07_1_4.txt;none;VUMC_HGCIN7
GSM4098888 CxSCC12 cell type:cervical squamous cell carcinoma; hpv:high-risk HPV-positive raw data file: US22502676_251485063646_S01_GE2-v5_95_Feb07_1_1.txt;none;VUMC_CxSCC12
GSM4098889 CxSCC15 cell type:cervical squamous cell carcinoma; hpv:high-risk HPV-positive raw data file: US22502676_251485063642_S01_GE2-v5_95_Feb07_1_4.txt;none;VUMC_CxSCC15
GSM4098890 CxSCC27 cell type:cervical squamous cell carcinoma; hpv:high-risk HPV-positive raw data file: US22502676_251485063645_S01_GE2-v5_95_Feb07_1_1.txt;none;VUMC_CxSCC27
GSM4098891 CxSCC28 cell type:cervical squamous cell carcinoma; hpv:high-risk HPV-positive raw data file: US22502676_251485063642_S01_GE2-v5_95_Feb07_1_3.txt;none;VUMC_CxSCC28
GSM4098892 CxSCC32 cell type:cervical squamous cell carcinoma; hpv:high-risk HPV-positive raw data file: US22502676_251485063643_S01_GE2-v5_95_Feb07_1_2.txt;none;VUMC_CxSCC32
GSM4098893 CxSCC36 cell type:cervical squamous cell carcinoma; hpv:high-risk HPV-positive raw data file: US22502676_251485063643_S01_GE2-v5_95_Feb07_1_1.txt;none;VUMC_CxSCC36
GSM4098894 CxSCC38 cell type:cervical squamous cell carcinoma; hpv:high-risk HPV-positive raw data file: US22502676_251485063644_S01_GE2-v5_95_Feb07_1_4.txt;none;VUMC_CxSCC38
GSM4098895 CxSCC39 cell type:cervical squamous cell carcinoma; hpv:high-risk HPV-positive raw data file: US22502676_251485063644_S01_GE2-v5_95_Feb07_1_3.txt;none;VUMC_CxSCC39
GSM4098874 HGCIN8 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063646_S01_GE2-v5_95_Feb07_1_3.txt;none;VUMC_HGCIN8
GSM4098875 HGCIN9 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063646_S01_GE2-v5_95_Feb07_1_4.txt;none;VUMC_HGCIN9
GSM4098876 HGCIN10 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063646_S01_GE2-v5_95_Feb07_1_4.txt;none;VUMC_HGCIN10
GSM4098877 HGCIN15 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063642_S01_GE2-v5_95_Feb07_1_3.txt;none;VUMC_HGCIN15
GSM4098878 HGCIN18 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063642_S01_GE2-v5_95_Feb07_1_1.txt;none;VUMC_HGCIN18
GSM4098879 HGCIN19 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063644_S01_GE2-v5_95_Feb07_1_2.txt;none;VUMC_HGCIN19
GSM4098880 HGCIN21 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063644_S01_GE2-v5_95_Feb07_1_2.txt;none;VUMC_HGCIN21
GSM4098881 HGCIN24 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063645_S01_GE2-v5_95_Feb07_1_1.txt;none;VUMC_HGCIN24
GSM4098882 HGCIN25 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063645_S01_GE2-v5_95_Feb07_1_3.txt;none;VUMC_HGCIN25
GSM4098883 HGCIN32 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063642_S01_GE2-v5_95_Feb07_1_2.txt;none;VUMC_HGCIN32
GSM4098884 HGCIN33 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063642_S01_GE2-v5_95_Feb07_1_2.txt;none;VUMC_HGCIN33
GSM4098885 HGCIN39 cell type:cervical intraepithelial neoplasia, grade 2-3; hpv:high-risk HPV-positive raw data file: US22502676_251485063643_S01_GE2-v5_95_Feb07_1_1.txt;none;VUMC_HGCIN39
GSM4098886 CxSCC2 cell type:cervical squamous cell carcinoma; hpv:high-risk HPV-positive raw data file: US22502676_251485063645_S01_GE2-v5_95_Feb07_1_2.txt;none;VUMC_CxSCC2
GSM4098887 CxSCC4 cell type:cervical squamous cell carcinoma; hpv:high-risk HPV-positive raw data file: US22502676_251485063646_S01_GE2-v5_95_Feb07_1_2.txt;none;VUMC_CxSCC4
Platform GPL4133  : Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
Literature 32188026  
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* p<0.05 ** p<0.01