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Aims and background <p>Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, and poses major treatment challenges due to its incompleteness, hazardous side effects and resistance to chemotherapy. In response, the use of molecular and targeted therapies to treat the disease is begin explored. We aimed in this study to investigate the effects of up- or down-regulation of the enhancer of zeste homolog 2 <i>(EZH2)</i> gene on the Wnt signaling pathway and on the invasiveness capacity of MKN-45 and AGS GC cell lines.</p> Material and methods <p>MKN-45 and AGS GC cell lines were transfected with <i>EZH2</i>-silencing and expression inducing vectors. RNA extraction and cDNA synthesis were performed to analyze the effect of <i>EZH2</i> on Wnt signaling by&#xa0;using RT-qPCR. Additionally, the transwell test was performed to assess cell invasion capacity of manipulated cells.</p> Results <p>The results showed that <i>EZH2</i> downregulation led to a significant decrease in expression of several involved genes in Wnt signaling pathway. Conversely, <i>EZH2</i> upregulation resulted in a meaningful increase in expression of Wnt genes, including <i>DVL1, CTNNB1 (β-catenin), VNT16, AXIN</i>, and <i>RNF43</i>. The expression of <i>LGR5</i> and <i>LEF1</i> genes showed an inverse relationship with <i>EZH2</i> up- and down-regulation. Additionally, the transwell assay demonstrated that up- and down-regulation of the <i>EZH2</i> gene had a direct effect on cell invasion in MKN-45 and AGS cell lines.</p> Conclusion <p>Our findings demonstrate the regulatory role of EZH2 on the Wnt signaling pathway in the GC and its contribution in tumor invasiveness. <i>EZH2</i> may be suggested as a potential therapeutic target to inhibit invasion of GC cell.</p>

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EZH2 regulates the invasiveness of gastric cancer probably by activating the Wnt signaling pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月1日

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  • Hosseinali Ghazvini,
  • Mohammad Mahdi Forghanifard,
  • Vajiheh Zarrinpour,
  • Shiva Mirkalantari

摘要

Aims and background

Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, and poses major treatment challenges due to its incompleteness, hazardous side effects and resistance to chemotherapy. In response, the use of molecular and targeted therapies to treat the disease is begin explored. We aimed in this study to investigate the effects of up- or down-regulation of the enhancer of zeste homolog 2 (EZH2) gene on the Wnt signaling pathway and on the invasiveness capacity of MKN-45 and AGS GC cell lines.

Material and methods

MKN-45 and AGS GC cell lines were transfected with EZH2-silencing and expression inducing vectors. RNA extraction and cDNA synthesis were performed to analyze the effect of EZH2 on Wnt signaling by using RT-qPCR. Additionally, the transwell test was performed to assess cell invasion capacity of manipulated cells.

Results

The results showed that EZH2 downregulation led to a significant decrease in expression of several involved genes in Wnt signaling pathway. Conversely, EZH2 upregulation resulted in a meaningful increase in expression of Wnt genes, including DVL1, CTNNB1 (β-catenin), VNT16, AXIN, and RNF43. The expression of LGR5 and LEF1 genes showed an inverse relationship with EZH2 up- and down-regulation. Additionally, the transwell assay demonstrated that up- and down-regulation of the EZH2 gene had a direct effect on cell invasion in MKN-45 and AGS cell lines.

Conclusion

Our findings demonstrate the regulatory role of EZH2 on the Wnt signaling pathway in the GC and its contribution in tumor invasiveness. EZH2 may be suggested as a potential therapeutic target to inhibit invasion of GC cell.