EZH2 loss promotes gastric squamous cell carcinoma [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1069735 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27743555_1.fastq.gz | Fastqsanger.gz | |||
| SRR27743555_2.fastq.gz | Fastqsanger.gz | |||
| SRR27743556_1.fastq.gz | Fastqsanger.gz | |||
| SRR27743556_2.fastq.gz | Fastqsanger.gz | |||
| SRR27743557_1.fastq.gz | Fastqsanger.gz |
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Project description:EZH2 loss promotes gastric squamous cell carcinoma
| PRJNA1069729 | ENA
Project description:Gastric Squamous Cell Carcinoma (GSCC) is a rare subtype of gastric cancer with unique histopathology while gastric adenosquamous carcinoma (GASC), which partially shares features of GSCC, is more frequent. Both GSCC and GASC have poor prognosis but the molecular mechanisms underlying these malignancies are unknown. Here, we performed genomics analyses of eleven GSCC samples and found that epigenetic regulation genes were among the most frequently mutated genes. Among them was Enhancer of zeste homolog 2 (EZH2), which was also significantly downregulated in GASC, compared to gastric adenocarcinoma (GAC). Ezh2 loss led to squamous feature both in gastric organoids in vitro and in vivo. Importantly, Ezh2 deficiency, together with Trp53 and Pten loss, both of which were also frequently mutated in GSCC, gave rise to full-blown GSCC in mice. Mechanistically, we found that Ezh2 could repress the expression of Transcription factor AP-2 gamma (Tfap2c), a transcription factor with the ability to initiate epidermal squamous differentiation, through H3K27 methylation. Disruption of Tfap2c reversed Ezh2 loss-driven GSCC into GAC and reduced its resistance to chemo treatment. Our study revealed the mechanisms of GSCC/GASC tumorigenesis and shed light on future treatment.
2025-05-18 | GSE254316 | GEO
Project description:Gastric Squamous Cell Carcinoma (GSCC) is a rare subtype of gastric cancer with unique histopathology while gastric adenosquamous carcinoma (GASC), which partially shares features of GSCC, is more frequent. Both GSCC and GASC have poor prognosis but the molecular mechanisms underlying these malignancies are unknown. Here, we performed genomics analyses of eleven GSCC samples and found that epigenetic regulation genes were among the most frequently mutated genes. Among them was Enhancer of zeste homolog 2 (EZH2), which was also significantly downregulated in GASC, compared to gastric adenocarcinoma (GAC). Ezh2 loss led to squamous feature both in gastric organoids in vitro and in vivo. Importantly, Ezh2 deficiency, together with Trp53 and Pten loss, both of which were also frequently mutated in GSCC, gave rise to full-blown GSCC in mice. Mechanistically, we found that Ezh2 could repress the expression of Transcription factor AP-2 gamma (Tfap2c), a transcription factor with the ability to initiate epidermal squamous differentiation, through H3K27 methylation. Disruption of Tfap2c reversed Ezh2 loss-driven GSCC into GAC and reduced its resistance to chemo treatment. Our study revealed the mechanisms of GSCC/GASC tumorigenesis and shed light on future treatment.
2025-05-18 | GSE254317 | GEO
Project description:EZH2 loss promotes gastric squamous cell carcinoma [CUT&Tag]
| PRJNA1069734 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-05-19 | GSE254318 | GEO
Project description:Background & Aims: E-cadherin expression disruption is commonly observed in epithelial cancers and metastasis. Such event is also recognized as a crucial step in gastric cancer (GC) initiation and progression. As aberrant expression of microRNAs often perturb the normal expression and function of pivotal cancer-related genes, we characterized and dissected a pathway initiated by loss of microRNA-101 that causes E-cadherin dysfunction through upregulation of EZH2 expression in GC. Methods: Microarrays were used to profile the expression of microRNAs in human GC. Array-CGH revealed DNA copy number changes that were validated by genomic quantitative PCR and Snapshot. Expression levels of microRNAs, mRNA and protein were determined by quantitative-real time PCR and western-blot/co-immunofluorescence. CDH1 inactivating mechanisms were analyzed. Gain and loss of function experiments were done in KatoIII cells. E-cadherin functionality was assessed by immunofluorescence and flow cytometry. Results: MiR-101 expression was significantly decreased in tumors in comparison with normal gastric mucosas (P<.0001). In 65% of the analyzed GC cases, miR-101 downregulation was caused by deletions and/or microdeletions at miR-101-2 locus. EZH2 overexpression and consequent loss/aberrant E-cadherin expression was found in concomitance with miR-101 downregulation in 41% of the analyzed GC cases. This occurred preferentially in cases retaining allele(s) untargeted by classical CDH1 inactivating mechanisms. MiR-101 gain of function experiments or direct inhibition of EZH2, led to a strong depletion of endogenous EZH2 protein and consequent rescue of functional E-cadherin at the cell membrane, mimicking results obtained with clinical GC samples. Conclusions: Deletions and/or microdeletions at miR-101-2 locus underlying mature miR-101 downregulation and consequent EZH2 overexpression represented a novel cascade of genetic events leading to E-cadherin disruption, preferentially affecting the intestinal-type of GC. In the present study, 37 primary GCs and a pool of 10 normal gastric mucosas were used to acquire the expression of 703 known human mature miRNAs deposited in the Sanger miRBase Sequence Database, Release 10.0 (http://microrna.sanger.ac.uk), as well as 393 novel human miRNAs discovered through deep sequencing and validated by qRT-PCR and array profiling (NCodeM-bM-^DM-" Human miRNA microarray probe set V3 from Invitrogen). The 10 normal gastric mucosa RNA samples were pooled to obtain the normal gastric reference sample, which was labelled and hybridised four times to check arrays' reproducibility.
2012-07-31 | E-GEOD-33743 | biostudies-arrayexpress
Project description:SAGE performed on biopsies of Barrett's esophagus, squamous esophagus and gastric cardia taken from a metaplastic Barrett's esophagus patient. Keywords: SAGE comparative analysis of gene expression profiles of Barrett's esophagus, normal squamous esophagus and gastric cardia tissue
2005-06-20 | E-GEOD-2769 | biostudies-arrayexpress
Project description:Rap1GAP is a critical tumor suppressor gene that is down-regulated in multiple aggressive cancers such as head and neck squamous cell carcinoma, melanoma and pancreatic cancer. However, the mechanistic basis of rap1GAP down-regulation in cancers is poorly understood. By employing an integrative approach, we demonstrate polycomb-mediated repression of rap1GAP that involves EZH2, a histone methyltransferase in head and neck cancers. We further concomitant down-regulation of rap1GAP in head and neck cancers. EZH2 represses rap1GAP by facilitating the trimethylation of H3K27, a mark of gene repression, and also hypermethylation of rap1GAP promoter. These results provide a conceptual framework involving a microRNA-oncogene-tumor suppressor axis to understand head and neck cancer progression. OSCC3-siRNA Non-Targeting Vs. siRNA EZH2 with dye-swap, HOK-Adeno CMV Vs. Adeno EZH2.
2011-11-02 | E-GEOD-28501 | biostudies-arrayexpress
Project description:Polycomb repressive complexes (PRC) play a critical role during tumorigenesis and development. The histone methyltransferase Enhancer of Zeste homologue 2 (EZH2), as a core component of PRC2, is frequently overexpressed in a wide variety of cancers. EZH2-mediated gene silencing contributes to carcinogenesis. To further the understanding of the EZH2 biology in gastric cancer, here we performed transcriptome analyses and identified EZH2-responsive genes upon EZH2 knockdown by RNA-seq.
2015-11-07 | E-MTAB-3227 | biostudies-arrayexpress