Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DeltaNp63 silencing, DNA methylation shifts and epithelial mesenchymal transition resulted from TAp63 genome editing in squamous cell carcinoma [RRBS]

ABSTRACT: TP63 (p63) is strongly expressed in lower-grade carcinomas of head-and-neck, skin, breast, urothelium, etc. to maintain the well-differentiated phenotype. TP63 has two transcription start sites at exon 1 and exon 3’ to produce TAp63 and DeltaNp63 isoforms, respectively. The major protein, DeltaNp63alpha, functions as a core factor to organize super enhancers of genes essential for epidermal/craniofacial differentiation and for self-activation of DeltaNp63. To examine whether very weakly expressed TAp63 has a specific role, we disrupted exon 1 by CRISPR-Cas9 homology directed repair (HDR) in a head and neck squamous cell carcinoma (SCC) line. Surprisingly, TAp63 knockout cells, with either ‘monoallelic HDR and a frameshift deletion on the other allele’ or ‘biallelic HDR’, caused DeltaNp63 silencing. Loss of keratinocyte-specific gene expression, replacement of KRT5 with VIM, and transcriptional suppression of cell-cell and cell-matrix adhesion components indicated core events of epithelial mesenchymal transition. Most of the positively and negatively impacted genes including DeltaNp63 displayed local CpG methylation changes. Furthermore, DeltaNp63 expression was partially rescued by transfection of TAp63alpha, followed by incubation with DNA methyltransferase inhibitor Zebularine. This study suggests that TAp63 is indispensable for DeltaNp63 expression by which keratinocyte-specific epigenome is maintained in SCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234979 | GEO | 2023/09/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

DeltaNp63 silencing, DNA methylation shifts and epithelial mesenchymal transition resulted from TAp63 genome editing in squamous cell carcinoma [microarray]

Project description:TP63 (p63) is strongly expressed in lower-grade carcinomas of head-and-neck, skin, breast, urothelium, etc. to maintain the well-differentiated phenotype. TP63 has two transcription start sites at exon 1 and exon 3’ to produce TAp63 and DeltaNp63 isoforms, respectively. The major protein, DeltaNp63alpha, epigenetically activates genes essential for epidermal/craniofacial differentiation, including DeltaNp63 itself. To examine whether weakly expressed TAp63 has a specific role, we disrupted exon 1 by CRISPR-Cas9 homology directed repair in a head and neck squamous cell carcinoma (SCC) line. Surprisingly, TAp63 knockout cells, either by monoallelic GFP cassette insertion paired with a frameshift deletion allele or by biallelic GFP cassette insertion, caused DeltaNp63 silencing. Loss of keratinocyte-specific gene expression, switching of intermediate filaments from KRT(s) to VIM, and suppression of cell-cell and cell-matrix adhesion components indicated core events of epithelial mesenchymal transition. Most of the positively and negatively impacted genes including DeltaNp63 displayed local DNA methylation changes. Furthermore, DeltaNp63 expression was partially rescued by transfection of TAp63alpha followed by incubation with DNA methyltransferase inhibitor Zebularine. TAp63, as a minor part of TP63 gene, may possibly be involved in the auto-activation mechanism of DeltaNp63 by which keratinocyte-specific epigenome is maintained in SCC.

2023-09-29 | GSE234978 | GEO

TAp63 in pancreas cancer predicts the squamous subtype and promotes a suppressive immune micromilleu

Project description:To evaluate the role of aberrant TAp63 in PDAC, we analyzed transcriptomics by RNAseq in the TAp63 and deltaNP63 over-expressing pancreatic cancer cells.

2022-11-22 | GSE218268 | GEO

Pimary human keratinocyte knockdown with deltaNp63 specific siRNA

Project description:Pimary human keratinocyte knockdown with deltaNp63 specific siRNA

| PRJNA683664 | ENA

Comparative analysis of algorithms for integration of copy number and expression data

Project description:Chromosomal instability is a hallmark of cancer and genes that display abnormal expression in chromosomally aberrant regions are likely to be key players in tumor progression. Identifying such driver genes from high-throughput data requires computational methods that are capable of integrating data from several sources and thereby enhance the reliability of driver gene identification. Hence, several algorithms that integrate copy number and expression data have been developed but their relative performance has not been assessed so far. We have compared 10 algorithms that integrate high-throughput copy number and transcriptomics data using simulated, cancer cell line and primary tumor data. Our results show that there are significant differences between the methods and their performance decreases significantly with small sample sets. Head and neck squamous cell carcinoma (HNSCC) cell lines from the tongue (UT-SCC-21,UT-SCC-24B, UT-SCC-30, UT-SCC-67, UT-SCC-73, UT-SCC-76A, UT-SCC-81, UT-SCC-87,UT-SCC-95) and larynx (UT-SCC-8, UT-SCC-11, UT-SCC-75) were provided by the Department of Otorhinolaryngology-Head and Neck Surgery at the Turku University Central Hospital (Turku, Finland). HNSCC cell lines SCC-4, SCC-9, SCC-25 and human skin keratinocyte HPV-16 E6/E7 transformed cell line CCD1106 KERTr was ordered from American Type Culture Collection (ATCC; Manassas, VA) and cultured according to the ATCC recommendations.

2012-02-10 | E-MEXP-3415 | biostudies-arrayexpress

RNA-seq of head and neck cell lines

Project description:Two HPV(+) head and neck cancer cell lines (UPCI-SCC-090, UM-SCC-104), one HPV(–) head and neck cancer cell line (FaDu) and one nasopharyngeal epithelial cell line (NP69SV40T) were subjected to RNA-seq analysis.

2023-01-06 | GSE211322 | GEO

miR-34a is downregulated in cis-diamminedichloroplatinum treated sinonasal squamous cell carcinoma patients with poor prognosis.

Project description:For the purpose of analyzing mechanisms related to the cis-diamminedichloroplatinum (CDDP) resistance in head and neck squamous cell carcinoma (head and neck SCC), we employed a nasal squamous cell carcinoma (nasal SCC) cell line RPMI2650 and its CDDP resistant substrain RPMI2650CR previously described. The identification of the resistance-related microRNA (miR) clusters was conducted between RPMI2650CR and RPMI2650 using microRNA microarray.

2012-06-14 | GSE32176 | GEO

A non-canonical Hippo pathway represses the expression of deltaNp63

Project description:Regulation of p63 expression occurs by a non-canonical version of the Hippo pathway in mammary epithelial, breast carcinoma and head and neck squamous carcinoma cells

2024-02-07 | GSE228680 | GEO

CSL ChIP-Seq on human keratinocytes

Project description:Down-modulation or loss-of-function mutations of the Notch 1 and 2 genes are associated with development of squamous cell carcinoma (SCC), a very frequent and therapy-resilient malignancy in skin, head/neck (H/N), lung and other surface epithelia. In this context, surprisingly little is known on the role of CSL (RBP-Jk), key effector of canonical Notch signaling endowed with intrinsic transcription repressive function. CSL expression is decreased in upper epidermal layers and differentiating primary human keratinocytes (HKCs), while it is up-regulated in premalignant and malignant SCC lesions and SCC cell lines from skin, Head/Neck and lung. Increased CSL levels enhance proliferation and self-renewal potential of HKCs and SCC cells, while its silencing induces growth arrest and apoptosis. In vivo, SCC cells with increased CSL levels give rise to rapidly expanding tumors, while upon CSL silencing they form smaller and more differentiated tumors with enhanced inflammatory infiltrate. Global transcriptomic analysis of HKC and SCC cells plus/minus CSL silencing reveals major modulation of apoptotic, cell cycle and pro-inflammatory genes, with no significant association with Notch or keratinocyte differentiation gene signatures. KDM6B, a histone demethylase gene with highly context dependent functions, is a direct CSL negative target, with an inverse role of CSL in HKC and SCC self-renewal and tumorigenesis, with IL6 as a target of likely significance. CSL / KDM6B protein expression could be used as biomarkers of SCC development and novel indicators of cancer treatment.

2017-12-15 | GSE102761 | GEO

CSL RNA-Seq on HKC and SCC cell lines

2017-12-15 | GSE102762 | GEO

miR-34a is downregulated in cis-diamminedichloroplatinum treated sinonasal squamous cell carcinoma patients with poor prognosis.

2012-06-13 | E-GEOD-32176 | biostudies-arrayexpress