A novel role for aspirin in enhancing the reprogramming function of miR-302/367 cluster and breast tumor suppression.

Abstract

Recent studies have provided evidence for tumor suppressive function of the embryonic stem cell-specific miR-302/367 cluster through induction of a reprogramming process. Aspirin has been found to induce reprogramming factors of mesenchymal-to-epithelial transition in breast cancer cells. Therefore, we aimed to investigate whether overexpression of miR-302/367 cluster and aspirin treatment cooperate in the induction of reprogramming and tumor suppression in breast cancer cells. MDA-MB-231 and SK-BR-3 human breast cancer cell lines were transfected with a miR-302/367 expressing vector and treated with aspirin. The cells were evaluated for indices of apoptosis, proliferation, migration, and invasion. In both cell lines, treatment of miR-302/367-transfected cells with aspirin upregulated expression of some main pluripotency factors such as OCT4, SOX2, NANOG, and KLF4, and downregulated expression of some invasion and angiogenesis markers at gene and protein levels. Aspirin increased the apoptotic rate in both cell lines transfected with miR-302/367. Both miR-302/367 and aspirin upregulated the expression of FOXD3 protein which is a known inducer of OCT4 and NANOG. Our results demonstrate that aspirin can enhance miR-302/367-induced reprogramming of breast cancer cells possibly through upregulation of FOXD3 expression. This can further augment the reversal of epithelial-mesenchymal transition and inhibits migration, invasion, and angiogenic signaling in breast cancer cells reprogrammed by miR-302/367. Therefore, aspirin may serve as a useful adjuvant for reprogramming of cancer cells.