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Increased expression of EHF via gene amplification contributes to the activation of HER family signaling and associates with poor survival in gastric cancer.

ABSTRACT: The biological function of E26 transformation-specific (ETS) transcription factor EHF/ESE-3 in human cancers remains largely unknown, particularly gastric cancer. The aim of this study was to explore the role of EHF in tumorigenesis and its potential as a therapeutic target in gastric cancer. By using quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays, we investigated the expression and copy number of EHF in a cohort of gastric cancers and control subjects. Specific EHF siRNAs was used to determine the biologic impacts and mechanisms of altered EHF expression in vitro and in vivo. Dual-luciferase reporter, chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) assays were performed to identify its downstream targets. Our results demonstrated that EHF was significantly upregulated and frequently amplified in gastric cancer tissues as compared with control subjects. Moreover, EHF amplification was positively correlated with its overexpression and significantly associated with poor clinical outcomes of gastric cancer patients. We also found that EHF knockdown notably inhibited gastric cancer cell proliferation, colony formation, migration, invasion and tumorigenic potential in nude mice and induced cell cycle arrest and apoptosis. Importantly, we identified EHF as a new HER2 transcription factor and the modulator of HER3 and HER4 in gastric cancer. Collectively, our findings suggest that EHF is a novel functional oncogene in gastric cancer by regulating the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases and may represent a potential prognostic marker and therapeutic target for this cancer.

SUBMITTER: Shi J

PROVIDER: S-EPMC5134001 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Increased expression of EHF via gene amplification contributes to the activation of HER family signaling and associates with poor survival in gastric cancer.

Shi Jing J Qu Yiping Y Li Xinru X Sui Fang F Yao Demao D Yang Qi Q Shi Bingyin B Ji Meiju M Hou Peng P

Cell death & disease 20161027 10

The biological function of E26 transformation-specific (ETS) transcription factor EHF/ESE-3 in human cancers remains largely unknown, particularly gastric cancer. The aim of this study was to explore the role of EHF in tumorigenesis and its potential as a therapeutic target in gastric cancer. By using quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays, we investigated the expression and copy number of EHF in a cohort of gastric cancers ...[more]

PMID: 27787520

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Project description:BackgroundMethyltransferase-like 3 (METTL3) expression could be found in various normal and cancerous tissues. As of now, the clinical significance of METTL3 expression in human pancreatic cancer (PC) tissues still remains to be understood. Our present study aims to investigate the prognostic value and clinical implications of METTL3 expression in PC tissues.MethodsThe TCGA, GTEx, and GEO public databases were used to study the mRNA expression level of the m6A family members and its relationship among PC tissues and normal pancreatic tissue. The immunohistochemistry was used to analyze the difference of METTL3 expression between cancer tissues and adjacent normal tissues. The prognostic value was evaluated by using the Log-rank survival analysis and Cox model analysis. PAAD samples from TCGA and GEO databases were used to perform the immune infiltration analysis and gene set enrichment analysis based on the genes that were highly correlated with METTL3.ResultsBased on the analysis of TCGA, GTEx, and GEO public database, we found that the m6A family members showed a higher correlation in PC tissues compared to normal pancreatic tissues, and the mRNA expression level of the m6A family members showed a significant difference between PC tissues and adjacent normal tissues. Moreover, scRNA-seq data indicated that METTL3 showed a higher expression level in malignant epithelial cells. Our immunohistochemistry results also confirmed that the intensity of METTL3 immunostaining in PC tissues was significantly higher than that in adjacent normal tissues (P = 0.015). The overall survival (OS) of PC patients with high expression of METTL3 protein were significantly poorer than those with low expression of METTL3 protein (HR = 1.788, 95% CI 1.071-2.984, P = 0.026). Further analysis of PC data from the database showed that METTL3 expression was associated with a variety of tumor-infiltrating immune cells and was involved in m6A modification and metabolism in PC tissues.ConclusionIncreased METTL3 expression at the protein level could be found in PC tissues, suggesting that the METTL3 expression was involved in the progression of PC and could serve as an important marker for prognostic prediction of this malignancy.

Dataset Information

Increased expression of EHF via gene amplification contributes to the activation of HER family signaling and associates with poor survival in gastric cancer.

Publications

Increased expression of EHF via gene amplification contributes to the activation of HER family signaling and associates with poor survival in gastric cancer.

Similar Datasets

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