HPV E7 binds Oct4 and regulates its activity in HPV-associated cervical cancers.
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB38189 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR4097830_1.fastq.gz | Fastqsanger.gz | |||
| ERR4097830_2.fastq.gz | Fastqsanger.gz | |||
| ERR4097831.fastq.gz | Fastqsanger.gz | |||
| ERR4097831_1.fastq.gz | Fastqsanger.gz | |||
| ERR4097831_2.fastq.gz | Fastqsanger.gz |
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Project description:The Octamer-binding transcription factor-4 (Oct4) is upregulated in different malignancies, yet a paradigm for mechanisms of Oct4 post-embryonic re-expression is inadequately understood. In cervical cancer, Oct4 expression is higher in HPV-related than HPV-unrelated cervical cancers and this upregulation correlates with the expression of the E7 oncogene. We have reported that E7 affects the Oct4-transcriptional output and Oct4-related phenotypes in cervical cancer, however, the underlying mechanism remains elusive. Here, we characterize the Oct4-protein interactions in cervical cancer cells and reveal that Methyl-binding proteins (MBD2 and MBD3), are determinants of Oct4 driven transcription. E7 triggers MBD2 downregulation and TET1 upregulation, thereby disrupting the methylation status of the Oct4 gene. This coincides with an increase in the total DNA hydroxymethylation leading to the re-expression of Oct4 in cervical cancer and likely affecting broader transcriptional patterns. Our findings reveal a previously unreported mechanism by which the E7 oncogene can regulate transcription by increasing DNA hydroxymethylation and lowering the barrier to cellular plasticity during carcinogenesis.
2023-12-11 | GSE248367 | GEO
Project description:E7 modulates Oct4 re-expression in cervical cancer
2023-04-06 | MSV000091651 | MassIVE
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:The study aimed to explore HPV E7-specific pathways in cervical cancer cells.
2024-08-25 | GSE274812 | GEO
Project description:To investigate the extent of host methylome dysregulation by the human papillomavirus (HPV) oncoprotein E7, we performed methylome array 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 | GSE83261 | GEO
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: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 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:Octamer binding transcription factor-4 (Oct4), is highly expressed in stem cells and has indispensable roles in pluripotency and cellular reprogramming. In contrast to other factors used for cellular reprogramming, a role for Oct4 outside embryonic stem cells has been elusive and highly controversial. Emerging evidence implicates Oct4 in the carcinogenic process, but the mechanism through which Oct4 may be functioning in cancers is not fully appreciated. Here, we provide evidence that Oct4 is expressed in human cervical cancer and this expression correlates with the presence of the human papillomavirus (HPV) oncogenes E6 and E7. Surprisingly, the viral oncogenes can complement exogenously provided Oct4 in reprogramming assays, providing functional validation for their ability to activate Oct4 transcription in Mouse Embryonic Fibroblasts (MEFs). To interrogate potential roles of Oct4 in cervical cancers we knocked-down Oct4 in HPV(+) (HeLa & CaSki) and HPV(-) (C33A) cervical cancer cell lines and found that Oct4 knockdown attenuated clonogenesis, only in the HPV(+) cells. More unexpectedly, cell proliferation and migration, were differentially affected in HPV(+) and HPV(-) cell lines. We provide evidence that Oct4 interacts with HPV E7 specifically at the CR3 region of the E7 protein and that introduction of the HPV oncogenes in C33A cells and human immortalised keratinocytes generates Oct4-associated transcriptional and phenotypic patterns, which mimic those seen in HPV(+) cells. We propose that a physical interaction of Oct4 with E7 regulates its activity in HPV(+) cervical cancers in a manner not seen in other cancer types.
| S-EPMC7228134 | biostudies-literature
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