Endothelin-3 is epigenetically silenced in endometrioid endometrial cancer

• Published in: Journal of cancer research and clinical oncology Vol. 149; no. 9; pp. 5687 - 5696
• Main Authors: Zmarzły, Nikola, Januszyk, Szymon, Mieszczański, Paweł, Morawiec, Emilia, Buda, Paulina, Dziobek, Konrad, Opławski, Marcin, Boroń, Dariusz
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2023; Springer Nature B.V
• Subjects: Cancer; Cancer Research; Carcinoma, Endometrioid - genetics; DNA methylation; DNA microarrays; Down-regulation; Endometrial cancer; Endometrial Neoplasms - genetics; Endometrium; Endothelin 3; Endothelin-1 - genetics; Endothelin-1 - metabolism; Endothelin-3 - genetics; Endothelin-3 - metabolism; Endothelins - genetics; Endothelins - metabolism; Epigenetics; Female; Gene Expression Regulation, Neoplastic; Hematology; Humans; Internal Medicine; Medicine; Medicine & Public Health; MicroRNAs; MicroRNAs - genetics; miRNA; mRNA; Oncology; Receptor, Endothelin A - genetics; DNA methylation; miRNA; Endothelins; Endometrial cancer; EDN3
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-022-04525-w

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.