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Endothelin-3 is epigenetically silenced in endometrioid endometrial cancer
Nikola Zmarzły1, Szymon Januszyk2, Paweł Mieszczański3
1Department of Histology, Cytophysiology and Embryology, Faculty of Medicine in Zabrze, Academy of Silesia in Katowice, Zabrze, Poland. nikola.zmarzly@gmail.com.
Purpose:
Changes in the activity of endothelins and their receptors may promote neoplastic processes. They can be caused by epigenetic modifications and modulators, but little is known about endothelin-3 (EDN3), particularly in endometrial cancer. The aim of the study was to determine the expression profile of endothelin family and their interactions with miRNAs, and to assess the degree of EDN3 methylation.
Methods:
The study enrolled 45 patients with endometrioid endometrial cancer and 30 patients without neoplastic changes. The expression profile of endothelins and their receptors was determined with mRNA microarrays and RT-qPCR. The miRNA prediction was based on the miRNA microarray experiment and the mirDB tool. The degree of EDN3 methylation was assessed by MSP.
Results:
EDN1 and EDNRA were overexpressed regardless of endometrial cancer grade, which may be due to the lack of regulatory effect of miR-130a-3p and miR-485-3p, respectively. In addition, EDN3 and EDNRB were significantly downregulated.
Conclusion:
The endothelial axis is disturbed in endometrioid endometrial cancer. The observed silencing of EDN3 activity may be mainly due to DNA methylation.
Insights
Endothelin-3 (EDN3) activity is silenced in endometrial cancer, likely due to DNA methylation. This finding sheds light on the role of endothelins in cancer development and epigenetic regulation.
Area of Science:
- Molecular biology
- Oncology
- Epigenetics
Background:
- Endothelin family members and their receptors play roles in neoplastic processes.
- Epigenetic modifications influence endothelin activity, but endothelin-3 (EDN3) in endometrial cancer remains understudied.
Purpose of the Study:
- To investigate the expression profile of the endothelin family and their receptor interactions with microRNAs (miRNAs) in endometrial cancer.
- To assess the methylation status of EDN3 in endometrioid endometrial cancer.
Main Methods:
- mRNA microarrays and RT-qPCR were used to determine endothelin and receptor expression in 45 endometrial cancer patients and 30 controls.
- miRNA prediction utilized microarray data and the mirDB tool.
- Methylation-specific PCR (MSP) assessed EDN3 methylation levels.
Main Results:
- Endothelin-1 (EDN1) and endothelin receptor type A (EDNRA) were overexpressed in endometrial cancer, potentially due to reduced regulation by miR-130a-3p and miR-485-3p.
- Endothelin-3 (EDN3) and endothelin receptor type B (EDNRB) showed significant downregulation.
- EDN3 silencing in endometrial cancer is strongly associated with DNA methylation.
Conclusions:
- The endothelin axis is disrupted in endometrioid endometrial cancer.
- DNA methylation appears to be the primary mechanism for the observed silencing of EDN3 activity.
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