MiR-519d and miR-328-3p Combinatorially Suppress Breast Cancer Progression

Background: MiR-519d and miR-328-3p had tumor-regulatory properties in different cancers, but their combinatorial effects and potential common target in breast cancer had not been fully reported. This research targeted to study the underlying mechanism of how miR-519d and miR-328-3p cooperatively suppressed breast cancer. Methods: MiR-519d and miR-328-3p expressions in breast cancer tissues and cells were assessed and Ki-67 expression was also checked. DLR assay was executed to verify whether Ki-67 was a common target of miR-519d and miR-328-3p. Western blot, flow cytometry, colony formation, wound healing and transwell assays were applied to examine the inhibitory roles of these two miRNAs on the malignant behaviors of breast cancer cells and the potential molecular mechanism. Results: Impeded miR-519d and miR-328-3p expressions and enhanced Ki-67 expression were detected in breast cancer tissues and cells. Ki-67 was confirmed as a target of these two miRNAs. MiR-519d and miR-328-3p hampered cell proliferation and blocked cell cycle via binding to Ki-67 and they also suppressed migration and invasion. The combinatorial effects of two miRNAs were much stronger than a single miRNA. Conclusion: Our findings proved that miR-519d and miR-328-3p played combinatorial anti-cancer roles in breast cancer by directly targeting a common target Ki-67. Our study suggested that these two miRNAs might own the potential to become novel therapeutic biomarkers involved in the diagnosis and therapy of breast cancer.