Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ecdysoneless protein regulates viral and cellular mRNA splicing to promote cervical oncogenesis

ABSTRACT: Ecdysoneless protein regulates viral and cellular mRNA splicing to promote cervical oncogenesis

PROVIDER: PRJNA729427 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Ecdysoneless protein regulates viral and cellular mRNA splicing to promote cervical oncogenesis

Project description:The high-risk subgroup of Human papilloma viruses (HPVs), exemplified by HPV16/18, are causally linked to human cancers of the anogenital tract, skin, and upper aerodigestive tract. The high-risk HPV oncoproteins E6 and E7 are expressed from a polycistronic transcript that can potentially give rise to alternatively spliced E6 mRNAs, a process important for E6 and E7 expression and oncogenic transformation. Previously, we identified ECD, the human homologue of the Drosophila ecdysoneless gene, as a novel HPV16 E6-interacting protein using Yeast two-hybrid system. Here, we show that the C-terminal region of ECD selectively binds to high-risk but not to low-risk HPV E6 proteins. We demonstrate that ECD is overexpressed in HPV+ as well as HPV- cervical and head and neck patient tumor samples. Using the TCGA dataset, we show that ECD mRNA overexpression predicts shorter survival in these cancer patients. Recent work from our laboratory showed that ECD associates with several components of RNA biogenesis/splicing machinery and are involved in mRNA export. Here, we show that ECD is an RNA binding protein and regulates mRNA splicing. RNAseq analyses of SiHa cells upon ECD knockdown (KD) revealed alterations of many cellular pathways with prominent downregulation of components of the mRNA splicing machinery. Further investigation revealed that ECD KD resulted in dysregulation of E6 RNA splicing, resulting in decreased E7 and increased RB protein. Furthermore, ECD KD dysregulated several cellular mRNAs known to be critical for HPV oncogenesis. Finally, we demonstrate that while ECD KD in cervical cancer cell lines led to a reduction in oncogenic traits, ECD overexpression together with E7 led to the immortalization of keratinocytes. Taken together, our results support a novel role of ECD in transcription and in viral and cellular mRNA splicing to support HPV-driven oncogenesis.

2022-06-01 | GSE174317 | GEO

Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer

Project description:We report that NEK2 protein level is overexpressed and correlated with the tumor stage and lymph node metastasis in cervical cancer. Furthermore, we provided evidence that NEK2-depleted cervical cancer cells exhibit impaired oncogenesis and enhanced radiosensitivity. Using RNA sequencing, we identify Wnt1 as a key downstream effector of NEK2. Knockdown of NEK2 downregulates the mRNA and protein levels of Wnt1, thereby inhibiting the activation of the Wnt/β-catenin signaling pathway. More importantly, the observed consequences induced by NEK2 depletion in cervical cancer cells can be partially rescued by Wnt1 overexpression. Taken together, these results demonstrate that NEK2 activates the Wnt/β-catenin signaling pathway via Wnt1 to drive oncogenesis and radioresistance in cervical cancer, indicating that NEK2 may be a promising target for the radiosensitization of cervical cancer.

2021-04-30 | GSE148531 | GEO

Viral integration transforms chromatin to drive oncogenesis

Project description:We report that the integration of the human papillomavirus into the host genome increases chromatin accessibility, transcription, and CTCF binding within 100 kbp of the integration site which promotes oncogenesis in some patients.

2020-02-14 | GSE143026 | GEO

Viral integration transforms chromatin to drive oncogenesis

Project description:Viral integration transforms chromatin to drive oncogenesis

| PRJNA598867 | ENA

Human Papillomavirus (HPV) genomic integration, expression and E6/E7 splicing patterns in cervical cancer associated with HPV16 or HPV18 infection

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

Glucose dissociates DDX21 dimers to regulate mRNA splicing and promote epidermal differentiation

Project description:We discovered that glucose directly bind to DDX21, induced the conformation change of the proteins and inhibit its helicase activity. Glucose also inhibits the dimerization of DDX21, re-localize DDX21 from nucleolus to nucleoplasm and reassemble DDX21 to RNA splicing complex. DDX21 is essential for epidermal differentiation while with normal glucose condition, DDX21 was re-localized from nucleolus to nucleoplasm, bind to splicing factors and mRNA introns more to regulate splicing of key differentiation factors and promote epidermal differentiation.

2023-01-05 | PXD028561 | Pride

Knock down of FTO in cervical cancer cells

Project description:FTO, an N6-methyladenosine (m6A) demethylase, can promote cervical cancer cell proliferation and migration. RNA-sequencing of SiHa cells with FTO knockdown was conducted to dissect the differentially expressed genes and the potential mechanism of FTO in cervical cancer.

2020-02-13 | GSE133517 | GEO

Daily temperature cycles promote alternative splicing of RNAs encoding SR45a, a splicing regulator in maize

Project description:Daily temperature cycles promote alternative splicing of RNAs encoding SR45a, a splicing regulator in maize

| PRJNA705177 | ENA

Mutations in splicing factor SF3B1 promote transformation through MYC stabilization

Project description:Mutations in splicing factor SF3B1 promote transformation through MYC stabilization

| PRJNA478381 | ENA