EYA2 upregulates miR-93 to promote tumorigenesis of breast cancer by targeting and inhibiting the STING signaling pathway

Abstract

Herein, we used DIANA TOOLS, GEPIA and other bioinformatics databases to predict regulatory pathways in breast cancer. Accordingly, we clarified the regulatory mechanism of EYA2 on miR-93 expression to aggravate breast cancer, which was involved with the STING signaling pathway. CCK-8 assay, scratch test, Transwell assay, and flow cytometry were applied to detect cell viability, migration, invasion, and apoptosis. The experimental data found that EYA2 was highly expressed in breast cancer tissues and cells and associated with poor prognosis. Overexpression of miR-93 in breast cancer was positively correlated with EYA2. EYA2 promoted miR-93 expression, advanced breast cancer cell proliferation and inhibited their apoptosis. Results of luciferase assay showed that miR-93 was enriched in the STING 3'UTR. Furthermore, knockdown of EYA2 inhibited the expression of miR-93, promoted the expression of STING, and inhibited the tumor growth. In response to EYA2 knockdown, the expression of IFN-β and ISG was increased, and PD-L1 was decreased. In addition, the phosphorylation level of TBK1 and IRF3 was enhanced, the percentage of myeloid-derived suppressor cells in blood was reduced, and secretion of IFN-β and IL-12 was enhanced. In conclusion, EYA2 upregulates miR-93 expression and promotes malignancy of breast cancer by targeting and inhibiting the STING signaling pathway.

Keywords: Apoptosis; Breast cancer; EYA2; Innate immunity; STING; miR-93.