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Updated: May 29, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
EZH2 Upregulates Notch Signaling Pathway Genes and Increases Cell Migration in Gastric Cancers
Hosseinali Ghazvini1, Mohammad Mahdi Forghanifard1, Vajiheh Zarrinpour1
1Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.
Abstract:
Gastric cancer, faced different therapeutic imperfections such as chemoresistance, dangerous side effects, and non-specificity of the treatments. Our aim in the present study was to investigate the potential of the Enhancer of Zeste Homolog 2 (EZH2) gene as a therapeutic target through analyzing its role in cell migration and regulation of Notch signaling pathway in gastric cancer. The overexpression and silencing studies of EZH2 gene were performed in MKN-45 and AGS gastric cancer cell lines using pCMV3-ORF-HA and RNAi-Ready pSIREN-RetroQ Retroviral vectors, respectively. The cell migration was assessed using wound healing and closure assays. The effect of EZH2 overexpression and silencing on the Notch signaling pathway was evaluated using real-time PCR. The EZH2 expression was directly correlated with the increased rate of cell migration. Furthermore, EZH2 increased expression of the majority of the Notch signaling pathway genes including MAML1, HES5, NOTCH1, NOTCH2, NOTCH3, HEY1, and HES1 in MKN-45 and AGS cells. EZH2, as an upstream regulator, enhances the cell migration capacity and modulate expression of Notch signaling pathway gene in gastric cancer. EZH2 may be considered as a proper target for the treatment of gastric cancer.
Insights
Enhancer of Zeste Homolog 2 (EZH2) promotes gastric cancer cell migration and influences Notch signaling pathway gene expression. Targeting EZH2 may offer a new therapeutic strategy for gastric cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Gastric cancer presents therapeutic challenges, including chemoresistance and side effects.
- The Enhancer of Zeste Homolog 2 (EZH2) gene's role in gastric cancer requires further investigation.
- Targeting specific genes offers potential for more effective gastric cancer therapies.
Purpose of the Study:
- To investigate EZH2 as a therapeutic target in gastric cancer.
- To analyze the role of EZH2 in gastric cancer cell migration.
- To evaluate EZH2's regulation of the Notch signaling pathway in gastric cancer.
Main Methods:
- EZH2 gene overexpression and silencing in MKN-45 and AGS gastric cancer cell lines.
- Assessment of cell migration using wound healing and closure assays.
- Evaluation of Notch signaling pathway gene expression via real-time PCR.
Main Results:
- EZH2 expression positively correlated with increased gastric cancer cell migration rates.
- EZH2 overexpression upregulated key Notch signaling pathway genes (MAML1, HES5, NOTCH1-3, HEY1, HES1).
- EZH2 acts as an upstream regulator, enhancing cell migration and modulating Notch pathway gene expression.
Conclusions:
- EZH2 significantly enhances gastric cancer cell migration capacity.
- EZH2 modulates the expression of genes within the Notch signaling pathway.
- EZH2 represents a promising therapeutic target for gastric cancer treatment.
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