The microRNA-27a: ZBTB10-specificity protein pathway is involved in follicle stimulating hormone-induced VEGF, Cox2 and survivin expression in ovarian epithelial cancer cells

Abstract

Previously, we demonstrated that follicle stimulating hormone (FSH) enhanced VEGF expression and facilitated ovarian cancer angiogenesis via the PI3K/AKT signaling pathway. In this study, we further investigated the involvement of microRNA-27a: ZBTB10-specificity protein pathway in the mechanism of FSH-induced VEGF, Cox2 and survivin expression. Treatment with FSH resulted in significant increase in the expression of VEGF, Cox2, survivin, Sp1 proteins and microRNA-27a in a dose-dependent manner, whereas reverse protein expression pattern was observed in ZBTB10. Downregulation of microRNA-27a using antisense microRNA-27a blocked FSH-induced VEGF, Cox2 and survivin expression. Overexpression of ZBTB10 also attenuated the FSH-induced expression of these molecules. The enhanced expression of VEGF, Cox2 and survivin was also abolished by knocking down Sp1 using small interfering RNA. Collectively, these results indicated that stimulation of ovarian cancer cell VEGF, Cox2 and survivin expression by FSH involves the microRNA-27a: ZBTB10-specificity protein pathway.