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Super-enhancer-driven CCAT1 is co-activated by SOX2 and TP63 and promotes squamous cancer from esophagus, head and neck and lung [RNA-seq]

ABSTRACT: Super-enhancer-driven CCAT1 is co-activated by SOX2 and TP63 and promotes squamous cancer from esophagus, head and neck and lung [RNA-seq]

PROVIDER: PRJNA417255 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6260750_1.fastq.gz	Fastqsanger.gz
	SRR6260750_2.fastq.gz	Fastqsanger.gz
	SRR6260744_1.fastq.gz	Fastqsanger.gz
	SRR6260744_2.fastq.gz	Fastqsanger.gz
	SRR6260745_1.fastq.gz	Fastqsanger.gz

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Super-enhancer-driven CCAT1 is co-activated by SOX2 and TP63 and promotes squamous cancer from esophagus, head and neck and lung [RNA-seq]

Project description:Squamous cell carcinomas (SCCs) are aggressive malignancies. Previous report demonstrated that the transcription factors TP63 and SOX2 exhibited overlapping genomic occupancy in SCCs. Our recent study have identified TP63 and SOX2 as super-enhancer-associated genes. However, functional consequences of their frequent co-localization at super-enhancers region remains unexplored. Here, ChIP-seq result indicated TP63 and SOX2 co-occupied peaks are significantly located the super enhancer region compare with unique of TP63 and SOX2 signaling, and combined RNA-seq analyses of different types of SCCs reveal that TP63 and SOX2 cooperatively regulate expression of the super-enhancer-associated the long non-coding RNA (lncRNA) gene, CCAT1. CCAT1 is highly expressed in SCCs compared to either other tumor types or normal tissues. CCAT1 expression strongly correlates with expression levels of TP63 and SOX2. Silencing of CCAT1 significantly reduces cellular growth both in vitro and in vivo, phenotyping the effect of silencing either TP63 or SOX2. Furthermore, ChIP-Seq and luciferase reporter assays demonstrate TP63 and SOX2 co-occupy the promoter and super-enhancer regions of CCAT1. Interaction of CCAT1 with TP63 and SOX2 are validated by RNA immunoprecipitation. In addition, ChIRP analysis suggests that CCAT1 regulates EGFR expression by binding to the super-enhancer of EGFR. Further investigations shows that CCAT1 activates both the MEK/ERK1/2 and PI3K/AKT signaling pathways through up-regulation of EGFR. In conclusion, CCAT1 is driven by master transcription factors TP63 and SOX2 and is recruited to the super-enhancer of EGFR, promoting SCC tumorigenesis through activation of the MEK/ERK1/2 and PI3K/AKT signaling pathways. These studies help to explain the pathogenesis of SCC and aids in providing novel therapeutic strategy.

2018-09-17 | GSE106564 | GEO

Super-enhancer-driven CCAT1 is co-activated by SOX2 and TP63 and promotes squamous cancer from esophagus, head and neck and lung [ChIP-seq]

2018-09-17 | GSE106563 | GEO

Super-enhancer-driven CCAT1 is co-activated by SOX2 and TP63 and promotes squamous cancer from esophagus, head and neck and lung

Project description:Super-enhancer-driven CCAT1 is co-activated by SOX2 and TP63 and promotes squamous cancer from esophagus, head and neck and lung

| PRJNA417249 | ENA

Super-enhancer-driven CCAT1 is co-activated by SOX2 and TP63 and promotes squamous cancer from esophagus, head and neck and lung [ChIP-seq]

Project description:Super-enhancer-driven CCAT1 is co-activated by SOX2 and TP63 and promotes squamous cancer from esophagus, head and neck and lung [ChIP-seq]

| PRJNA417252 | ENA

SOX2 is required for foregut squamous epithelial homeostasis and lost during Barrett’s esophagus development

Project description:Esophageal adenocarcinoma (EA) is increasingly common. EA is thought to arise from a precursor lesion, Barrett’s esophagus (BE), in which chronic bile and acid reflux from the stomach injures the esophagus and induces the esophageal squamous epithelium to transition to a mixed gastric and intestinal glandular mucosa. The molecular determinants driving this metaplasia are poorly understood. We established a biobank of human patient-derived BE organoids that recapitulated the molecular heterogeneity of BE. Bulk and single-cell transcriptomics, corroborated with analysis of patient tissues, pointed to BE differentiation depending on a balance between two transcription factors that govern foregut versus hindgut embryonic gastrointestinal development: SOX2 (driving esophageal and stomach differentiation) and CDX2 (driving intestinal differentiation). Using squamous-specific inducible Sox2 knockout (Krt5CreER/+; Sox2Δ/Δ;ROSA26LSLTdTomato/+) mice, we found increased basal proliferation and decreased differentiation in the foregut squamous epithelium. Remarkably, Sox2Δ/Δ mice also harbored expanded glands at the squamocolumnar junction, some of which lineage traced to Krt5-expressing cells, indicating metaplasia from squamous epithelium. CUT&RUN analysis showed SOX2 bound and promoted differentiation-associated (e.g.,Krt13) and repressed proliferation-associated (e.g., Mki67) targets. Thus, SOX2 is critical for foregut squamous epithelial differentiation and its decreased expression likely an initiating step in progression to BE and thence to EA.

2025-06-07 | PXD063992 | Pride

Differential gene expression by suppression of either SOX2 or TP63 in KYSE70 human esophageal squamous carcinoma cell line.

Project description:SOX2 is a transcription factor essential for pluripotent stem cells, and development and maintenance of squamous epithelium. We previously reported SOX2 an oncogene subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs)1. Here we demonstrate in SCCs that SOX2 interacts with another master squamous transcription factor p63, and through ChIP-seq show that genomic occupancy of SOX2 overlaps with that of p63 at a large number of loci and that they cooperatively regulate gene expression including ETV4, which we find essential for SOX2-amplified SCC cell survival. Furthermore, SOX2 binds to distinct genomic loci in SCCs than in embryonic stem cells and the SOX2-p63 coordinate binding is unique to SCC. In addition, a subset of SOX2 genomic binding sites in SCC that lack p63 co-occupancy are co-occupied by the AP-1 transcriptional complex. These demonstrate that SOX2M-bM-^@M-^Ys actions in SCC differ substantially from its role in pluripotency and identify novel SOX2 interactions that will enable deeper characterization of SOX2M-bM-^@M-^Ys function in SCC. KYSE70 cells with stable expression of either pLKO-Tet-Op-shSOX2 or pLKO-Tet-Op-shTp63 were treated with 50ng/ml of doxycyline for 4 days. Total RNA was extracted, polyA+ selected, reverse transcribed, library constructed and sequencing was performed with Illumina HiSeq 2000. Differencial gene expression between the stable cell lines with Dox-induced and non-Dox treated was analyzed to determine the effects by suppression of either SOX2 or TP63 in KYSE70 cells.

2014-05-13 | E-GEOD-47058 | biostudies-arrayexpress

Loss of SOX2 expression induces cell migration via Vimentin up-regulation and serves as unfavourable risk factor for poor survival of head and neck squamous cell carcinoma patients

2014-09-23 | GSE61599 | GEO

Loss of SOX2 expression induces cell migration via Vimentin up-regulation and serves as unfavourable risk factor for poor survival of head and neck squamous cell carcinoma patients

Project description:Transcriptional profiling of patient derived HNSCC (head and neck squamous cell carcinoma) cell line HNO223 comparing control cells transfected with shRNA against luciferase (shLuci) with cells transfected with two different shRNAs targeting SOX2. The goal was to determine the effects of SOX2 knockdown on global gene expression. Total RNA was extracted from stably transfected HNSCC cells with shLuci (control) and two different SOX2 shRNAs (shSOX2#1 and shSOX2#2), comparing the control with each of the two SOX2 shRNAs (replicate1: shLuci vs. shSOX2#1 and replicate2: shLuci vs. shSOX2#2). The biological replicates were from two independent transfection experiments (transfection 1 and transfection 2). Gene expression profiling was performed using the Human GE 4x44K v2 Microarray according to manufacturer`s instructions (Agilent, Santa Clara, CA).

2014-09-23 | E-GEOD-61599 | biostudies-arrayexpress

SOX2 regulates foregut squamous epithelial homeostasis and is lost during Barrett’s esophagus development [CUT&Run]

Project description:Esophageal adenocarcinoma (EA) is increasingly prevalent and is thought to arise from Barrett’s esophagus (BE), a metaplastic condition in which chronic acid and bile reflux transforms the esophageal squamous epithelium into a gastric-intestinal glandular mucosa. The molecular determinants driving this metaplasia are poorly understood. We developed a human BE organoid biobank that recapitulates BE’s molecular heterogeneity. Bulk and single-cell transcriptomics, supported by patient tissue analysis, revealed that BE differentiation reflects a balance between SOX2 (foregut/esophageal) and CDX2 (hindgut/intestinal) transcription factors. Using squamous-specific inducible Sox2 knockout (Krt5CreER/+; Sox2∆/∆; ROSA26tdTomato/+) mice, we observed increased basal proliferation, reduced squamous differentiation, and expanded metaplastic glands at the squamocolumnar junction, some tracing back to Krt5-expressing cells. CUT&RUN analysis showed SOX2 bound and promoted differentiation-associated (e.g., Krt13) and repressed proliferation-associated (e.g., Mki67) targets. Thus, SOX2 is critical for foregut squamous epithelial differentiation and its decreased expression is likely an initiating step in progression to BE and thence to EA.

2025-06-06 | GSE297942 | GEO

SOX2 regulates foregut squamous epithelial homeostasis and is lost during Barrett’s esophagus development [scRNA-seq]

2025-06-06 | GSE298632 | GEO