Etoposide-induced MicroRNA-205-5p Suppresses Proliferation and Migration by Targeting ERBB4 in MCF-7 Cells

Abstract

Background/aim: Patients with breast cancer frequently encounter a dismal prognosis due to the lack of effective and curative therapies. MicroRNAs (miRNAs) are aberrantly regulated in many types of cancer and have been recognized to play crucial roles in cancer progression. We performed a preclinical investigation of the anti-cancer effect of etoposide and microRNA-205-5p (miRNA-205-5p) and their relationship in MCF-7 cells.

Materials and methods: Two cell culture systems, namely monolayers and spheroids, were employed for evaluating the effect of etoposide and miRNA-205-5p on cell proliferation and migration. Real time quantitative polymerase chain reaction was used for the measurement of mRNA and miRNA levels. Luciferase and western blot assays were utilized for the validation of the target gene of miRNA-205-5p.

Results: Treatment with etoposide, suppressed both cell proliferation and migration in MCF-7 monolayers. Also, the growth of MCF-7 spheroids as demonstrated by size measurements was inhibited by etoposide treatment. Furthermore, etoposide was found to upregulate the level of miRNA-205-5p. Over-expression of miRNA-205-5p inhibits cell proliferation and migration by directly targeting Erb-B2 receptor tyrosine kinase 4 (ERBB4).

Conclusion: miRNA-205-5p may act as an important mediator of the anti-cancer effect of etoposide and miRNA-205-5p-based therapy may expand the therapeutic opportunities for breast cancer.

Keywords: ERBB4; Etoposide; breast cancer; miRNA-205-5p; microRNA; spheroid.