Host chromatin architecture constrains the cis-regulatory effect of HPV integrations in cervical tumors.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE247605 | GEO | 2023/11/18
REPOSITORIES: GEO
Similar Datasets
Project description:We perfomed RNA-seq analysis using HPV18-postive HeLa cells for HPV integration and expression analyses
2021-03-25 | GSE165475 | GEO
Project description:We perfomed RNA-seq analysis using HPV16-postive CaSki and SiHa cells and HPV18-postive HeLa cells for HPV integration and gene expression analyses
2022-03-30 | GSE158033 | 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
Project description:This study assessed the transcriptional profile of SiHa cells. SiHa is a cervical cancer cell line with integrated HPV16, and was used as a model to study human gene expression in the context of integrated virus. Gene expression in SiHa, calculated by Cufflinks, was scored in windows around the locations of known viral integrations in patients or cell lines to determine if there was an association between gene expression and viral integration. We found that SiHa gene expression was higher near loci of integration for HPV18 vs. HPV16, cervical tissues vs. head and neck cancers, and cervical cancers vs. in vitro integrations. This study provides insight into the factors that may influence where viruses integrate in the human genome.
2015-11-30 | GSE67115 | GEO
Project description:Identification of genes differentially expressed in tumorigenic compared to non-tumorigenic, HPV18 positive cells Keywords: ordered We used microarrays to identify genes differentially expressed in tumorigenic HeLa x fibroblast hybrid cells (CGL3) and parental HeLa cells compared to non-tumorigenic HeLa x fibroblast hybrid cells (444). Gene expression profiles of proliferating cells under cell culture conditions were compared to identify differential gene expression patterns of upregulated and downregulated mRNA expression patterns of tumorigenic CGL3 and HeLa cells versus non-tumorigenic 444 cells..
2013-11-27 | E-GEOD-14052 | biostudies-arrayexpress
Project description:Background: Disruptions of 3D chromatin architecture can alter the activity of topologically associated domains (TADs), rewire enhancer-promoter interactions and thus significantly impact gene regulatory programs. Recently, such disruptions have been implicated in tumorigenesis, highlighting the need for a deeper understanding of their detailed role. Methods: T-ALL primary samples and prototypical cell lines as well as healthy T cell counterparts were profiled by in-situ Hi-C, RNA-Seq and CTCF ChIP-Seq. Data was subsequently integrated. Results: Our studies showed that the genome of leukemia cells does not display global changes in TAD structures but presents local changes in selected TAD boundaries as well as alterations of intra-TAD activity which are associated with changes in gene expression of key oncogenes and tumor suppressors, strong correlation with CTCF-mediated insulation and enhancer activity. Finally, we showed that 3D interactions on selected loci can be partially corrected pharmacologically, potentially accounting for the anti-leukemogenic effects of these drugs. Conclusions: Our studies underscore the need for further investigation of factors that rewire long range interactions especially during tumorigenesis, as they could be targets for pharmacological targeting.
2019-08-04 | GSE134762 | GEO
Project description:Background: Disruptions of 3D chromatin architecture can alter the activity of topologically associated domains (TADs), rewire enhancer-promoter interactions and thus significantly impact gene regulatory programs. Recently, such disruptions have been implicated in tumorigenesis, highlighting the need for a deeper understanding of their detailed role. Methods: T-ALL primary samples and prototypical cell lines as well as healthy T cell counterparts were profiled by in-situ Hi-C, RNA-Seq and CTCF ChIP-Seq. Data was subsequently integrated. Results: Our studies showed that the genome of leukemia cells does not display global changes in TAD structures but presents local changes in selected TAD boundaries as well as alterations of intra-TAD activity which are associated with changes in gene expression of key oncogenes and tumor suppressors, strong correlation with CTCF-mediated insulation and enhancer activity. Finally, we showed that 3D interactions on selected loci can be partially corrected pharmacologically, potentially accounting for the anti-leukemogenic effects of these drugs. Conclusions: Our studies underscore the need for further investigation of factors that rewire long range interactions especially during tumorigenesis, as they could be targets for pharmacological targeting.
2019-08-04 | GSE134761 | GEO
Project description:Background: Disruptions of 3D chromatin architecture can alter the activity of topologically associated domains (TADs), rewire enhancer-promoter interactions and thus significantly impact gene regulatory programs. Recently, such disruptions have been implicated in tumorigenesis, highlighting the need for a deeper understanding of their detailed role. Methods: T-ALL primary samples and prototypical cell lines as well as healthy T cell counterparts were profiled by in-situ Hi-C, RNA-Seq and CTCF ChIP-Seq. Data was subsequently integrated. Results: Our studies showed that the genome of leukemia cells does not display global changes in TAD structures but presents local changes in selected TAD boundaries as well as alterations of intra-TAD activity which are associated with changes in gene expression of key oncogenes and tumor suppressors, strong correlation with CTCF-mediated insulation and enhancer activity. Finally, we showed that 3D interactions on selected loci can be partially corrected pharmacologically, potentially accounting for the anti-leukemogenic effects of these drugs. Conclusions: Our studies underscore the need for further investigation of factors that rewire long range interactions especially during tumorigenesis, as they could be targets for pharmacological targeting.
2019-08-04 | GSE115893 | GEO
Project description:Background: Disruptions of 3D chromatin architecture can alter the activity of topologically associated domains (TADs), rewire enhancer-promoter interactions and thus significantly impact gene regulatory programs. Recently, such disruptions have been implicated in tumorigenesis, highlighting the need for a deeper understanding of their detailed role. Methods: T-ALL primary samples and prototypical cell lines as well as healthy T cell samples were profiled by in-situ Hi-C, RNA-Seq, CTCF ChIP-Seq and suuported by matching WGS of three primary T-ALL samples. Data was subsequently integrated. Results: Our studies showed that the genome of leukemia cells does not display global changes in TAD structures but presents local changes in selected TAD boundaries as well as alterations of intra-TAD activity which are associated with changes in gene expression of key oncogenes and tumor suppressors, strong correlation with CTCF-mediated insulation and enhancer activity. Finally, we showed that 3D interactions on selected loci can be partially corrected pharmacologically, potentially accounting for the anti-leukemogenic effects of these drugs. Conclusions: Our studies underscore the need for further investigation of factors that rewire long range interactions especially during tumorigenesis, as they could be targets for pharmacological targeting.
2019-10-29 | GSE139449 | GEO
Project description:Background: Disruptions of 3D chromatin architecture can alter the activity of topologically associated domains (TADs), rewire enhancer-promoter interactions and thus significantly impact gene regulatory programs. Recently, such disruptions have been implicated in tumorigenesis, highlighting the need for a deeper understanding of their detailed role. Methods: T-ALL primary samples and prototypical cell lines as well as healthy T cell counterparts were profiled by in-situ Hi-C, RNA-Seq and CTCF ChIP-Seq. Data was subsequently integrated. Results: Our studies showed that the genome of leukemia cells does not display global changes in TAD structures but presents local changes in selected TAD boundaries as well as alterations of intra-TAD activity which are associated with changes in gene expression of key oncogenes and tumor suppressors, strong correlation with CTCF-mediated insulation and enhancer activity. Finally, we showed that 3D interactions on selected loci can be partially corrected pharmacologically, potentially accounting for the anti-leukemogenic effects of these drugs. Conclusions: Our studies underscore the need for further investigation of factors that rewire long range interactions especially during tumorigenesis, as they could be targets for pharmacological targeting.
2019-08-04 | GSE115895 | GEO