High-risk human papillomavirus E7 affects host keratinocyte DNA methylation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE83261 | GEO | 2017/06/11
SECONDARY ACCESSION(S): PRJNA325447
REPOSITORIES: GEO
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Project description:To investigate the extent of gene expression dysregulation by the human papillomavirus (HPV) oncoprotein E7, we performed global gene expression analysis on normal immortalized keratinocytes from skin (NIKS), NIKS cells maintaining the HPV16 or 18 episomes (NIKS-16, NIKS-18, respectively), and NIKS cells maintaining the HPV-16 episome deficient in E7 expression (NIKS-16ΔE7).
2017-06-11 | GSE83259 | GEO
Project description:Acute expression of E7 oncogene from HPV-16 or HPV-18 is sufficient to overcome tumor necrosis factor-alfa (TNF) cytostatic effect on primary human keratinocytes. In the present study we investigated the molecular basis of E7-induced TNF resistance through a comparative analysis of the effect of this cytokine on the proliferation and global gene expression of organotypic cultures of normal and E7(wild type or mutant)-expressing keratinocytes.
2010-01-15 | GSE17892 | GEO
Project description:Acute expression of E7 oncogene from HPV-16 or HPV-18 is sufficient to overcome tumor necrosis factor-alfa (TNF) cytostatic effect on primary human keratinocytes. In the present study we investigated the molecular basis of E7-induced TNF resistance through a comparative analysis of the effect of this cytokine on the proliferation and global gene expression of organotypic cultures of normal and E7(wild type or mutant)-expressing keratinocytes. In order to determine the effects of E7 expression on TNF response, we performed 3 independent experiment for each cell line. Organotypic cultures of normal and E7(wild type or mutant)-expressing keratinocytes were treated with 2 nM TNF for 72 hours, or left untreated.
2010-06-24 | E-GEOD-17892 | biostudies-arrayexpress
Project description:The life cycle of human papillomaviruses (HPV) is strictly linked to the differentiation of their natural host cells. The HPV E6 and E7 oncoproteins can delay the normal differentiation program of keratinocytes, however, the exact mechanisms responsible for this have not yet been identified. The goal of this study was to investigate the effects of HPV16 oncoproteins on the expression of genes involved in keratinocyte differentiation. Primary human keratinocytes transduced by LXSN (control) retroviruses or virus vectors expressing HPV16 E6, E7 or E6/E7 genes were subjected to gene expression profiling. The results of microarray analysis showed that HPV 16 E6 and E7 have the capacity to down-regulate the expression of several genes involved in keratinocyte differentiation. Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to confirm microarray data. To investigate the effects of the HPV oncoproteins on the promoters of selected keratinocyte differentiation genes, luciferase reporter assays were performed. Our results suggest that the HPV 16 E6 and/or E7 oncogenes are able to down-regulate the expression of several genes involved in keratinocyte differentiation, at least partially by down-regulating their promoter activity. This activity of the HPV oncoproteins may have a role in the productive virus life cycle, and also in virus induced carcinogenesis. Primary human foreskin keratinocytes were transduced by retrovirus vectors containing HPV 16 E6, E7, E6/E7 or the control vector LXSN. The global gene expression patterns of transduced keratinocytes were analyzed on Affymetrix microarrays
2014-06-26 | E-GEOD-58841 | biostudies-arrayexpress
Project description:Specific types of human papillomaviruses (HPVs) cause cervical cancer, the second most common tumor in females worldwide. Both cellular transformation and the maintenance of the oncogenic phenotype of HPV-positive tumor cells are linked to the expression of the viral E6 and E7 oncogenes. In order to identify downstream cellular target genes for the viral oncoproteins, we silenced endogenous E6 and E7 expression in HPV-positive HeLa cells by RNA interference (RNAi). Subsequently, we assessed changes of the cellular transcriptome by genome-wide microarray analysis. We identified, 648 genes wich were either downregulated (360 genes) or upregulated (288 genes) upon inhibition of E6/E7 expression. A large fraction of these genes is involved in tumour-relevant processes, such as apoptosis control, cell cycle regulation, or spindle formation. Others may represent novel cellular targets for the HPV oncogenes, such as a large group of C-MYC-associated genes involved in RNA splicing. Keywords: siRNA mediated knockdown
2007-07-01 | GSE6926 | GEO
Project description:The life cycle of human papillomaviruses (HPV) is strictly linked to the differentiation of their natural host cells. The HPV E6 and E7 oncoproteins can delay the normal differentiation program of keratinocytes, however, the exact mechanisms responsible for this have not yet been identified. The goal of this study was to investigate the effects of HPV16 oncoproteins on the expression of genes involved in keratinocyte differentiation. Primary human keratinocytes transduced by LXSN (control) retroviruses or virus vectors expressing HPV16 E6, E7 or E6/E7 genes were subjected to gene expression profiling. The results of microarray analysis showed that HPV 16 E6 and E7 have the capacity to down-regulate the expression of several genes involved in keratinocyte differentiation. Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to confirm microarray data. To investigate the effects of the HPV oncoproteins on the promoters of selected keratinocyte differentiation genes, luciferase reporter assays were performed. Our results suggest that the HPV 16 E6 and/or E7 oncogenes are able to down-regulate the expression of several genes involved in keratinocyte differentiation, at least partially by down-regulating their promoter activity. This activity of the HPV oncoproteins may have a role in the productive virus life cycle, and also in virus induced carcinogenesis.
2014-06-26 | GSE58841 | GEO
Project description:The human papillomavirus virus (HPV) is a proven cause of most human cervical cancers, and might have a role in other malignancies including vulva, skin, oesophagus, head and neck cancer. HPV has also been speculated to have a role in the pathogenesis of lung cancer. To validate the hypothesis of HPV involvement in small cell lung cancer pathogenesis we performed gene expression profile of transgenic mouse model of SCLC induced by HPV-16 E6/E7 oncoproteins. Gene expression profile of SCLC has been performed using Agilent whole mouse genome (4x44k) representing ~ 41000 genes and mouse transcripts. Samples were obtained from two HPV16-E6/E7 transgenic mouse model and from littermateM-bM-^@M-^Ys normal lung.
2014-05-27 | E-GEOD-23962 | biostudies-arrayexpress
Project description:The human papillomavirus virus (HPV) is a proven cause of most human cervical cancers, and might have a role in other malignancies including vulva, skin, oesophagus, head and neck cancer. HPV has also been speculated to have a role in the pathogenesis of lung cancer. To validate the hypothesis of HPV involvement in small cell lung cancer pathogenesis we performed gene expression profile of transgenic mouse model of SCLC induced by HPV-16 E6/E7 oncoproteins.
2014-05-27 | GSE23962 | GEO
Project description:This analysis was performed with the aim of finding the genes differentially expressed in fibroblasts transduced with the E6/E7 genes of HPV 16, 18, 38b, 107 and 122. The name given for the samples are as follows: FB-E6E7-16, FB-E6E7-18, FB-E6E7-38b, FB-E6E7-107, FB-E6E7-122, and for fibroblasts transduced with the empty lentiviral vector pLVX, they were referred as FB-pLVX. Methods: Library construction and Illumina NovaSeq 6000 sequencing was performed by Novogene Bioinformatics Technology Co., Ltd, Beijing, China, on HPV 16, 18, 38b, 107 and 122 E6E7 Transduced Fibroblasts; three independently mRNA sequences were performed for each of the cell models. Bioinformatics analyses were performed as follows: raw reads were analyzed using the open source Galaxy platform (https://www.usegalaxy.org) and RStudio software (2021.09.0). The quality of the reads was checked using the FastQC tool, and the Trimmomatic tool was used to remove ambiguous nucleotides. Subsequently, all clean reads were mapped to the human genome reference (hg38 vs 38) using Rsubread for RStudio. Once all BAM files were obtained, reads were counted using the featureCounts tool, and gene expression analysis was performed using the DESeq2 tool. The gene expression level was normalized using the fragments per kilobase of transcript per million mapped reads (FPKM) method. Data validation was performed by real-time PCR. Conclusions: Our study represents the first analysis of genes differentially expressed by the E6/E7 proteins of HPV genus Beta-2 (38b, 107 and 122), through RNA-seq technology. This study shows the transforming potential that genotypes of the Beta-2 genus, especially HPV122, also possess. These Beta-2 HPVs can modulate some of the genes that are well known to be regulated by Alpha-HPVs 16 and 18.
2022-07-21 | GSE191090 | GEO
Project description:Human papillomavirus (HPV) genome integration into the host genome, blocking E2 expression and leading to overexpression of E6 and E7 viral oncogenes, is considered a major step in cervical cancer development. In high-risk HPVs, E6 and E7 oncogenes are expressed as a bicistronic pre-mRNA, with alternative splicing producing the ultimate mRNAs required for E6 and E7 translation. Given the number of alternative donor and acceptor splicing sites, ten E6/E7 different alternative transcripts might be formed for HPV16 and three for HPV18, although only six isoforms have been previously reported for HPV16. In the present work, we employ high-throughput sequencing of invasive cervical cancer transcriptome (RNA-Seq) to characterize the expression of the HPV genome in 24 invasive cervical cancers associated with HPV16 and HPV18 single infections. Based on high-resolution transcriptional maps, we herein report three viral gene expression patterns which might be associated with the presence of the viral genome in episomal and/or integrated stages. Alternative mRNAs splicing isoforms coding for E6 and E7 oncoproteins were characterized and quantified, and two novel isoforms were identified. Three major isoforms (E6*I, E6*II, and E6+E7) were detected for HPV16 and two for HPV18 (E6*I and E6+E7). Minor transcript isoforms, including the novel ones, were very rare in some tumor samples or were not detected. Our data suggested that minor transcript isoforms of E6/E7 do not play a relevant role in cervical cancer.
2019-08-06 | GSE91065 | GEO