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

EYA2 upregulates miR-93 and promotes breast cancer. miR-93 targets and suppresses STING. miR-93 regulates STING signaling pathway. EYA2 promotes tumorigenesis through miR-93. Knocking down EYA2 activates autoimmunity in breast cancer cells. Herein, we used DIANA TOOLS, gene expression profiling interactive analysis and other bioinformatics databases to predict regulatory pathways in breast cancer. Accordingly, we clarified the regulatory mechanism of eyes absent family of protein (EYA2) on miR-93 expression to aggravate breast cancer, which was involved with the STING signaling pathway. Cholecystokinin octapeptide 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 (untranslated region). 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-beta and interferon-stimulated gene was increased, and PD-L1 was decreased. In addition, the phosphorylation level of TANK-binding kinase 1 and interferon regulatory factor 3 was enhanced, the percentage of myeloid-derived suppressor cells in blood was reduced, and secretion of IFN-beta 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.