The microRNA-27a: ZBTB10-specificity protein pathway is involved in follicle stimulating hormone-induced VEGF, Cox2 and survivin expression in ovarian epithelial cancer cells
The microRNA-27a: ZBTB10-specificity protein pathway is involved in follicle stimulating hormone-induced VEGF, Cox2 and survivin expression in ovarian epithelial cancer cells
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DOI：
10.3892/ijo.2012.1743
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发表时间：
2013-02-01
影响因子：
5.2
通讯作者：
Feng, Youji
中科院分区：
文献类型：
--
作者：
Lai, Yunli;Zhang, Xuerong;Feng, Youji
在此之前，我们通过PI3K/AKT信号通路证实了卵泡刺激素(FSH)促进了VEGF的表达，促进了卵巢癌血管生成。在本研究中，我们进一步研究了microRNA-27A：ZBTB10特异性蛋白通路在FSH诱导的VEGF、COX2和Survivin表达机制中的作用。经FSH处理后，VEGF、COX2、Survivin、Sp1蛋白和microRNA-27A的表达显著增加，且呈剂量依赖关系，而ZBTB10的蛋白表达则相反。用反义microRNA-27A下调microRNA-27A可阻断FSH诱导的VEGF、COX2和Survivin的表达。ZBTB10的过表达也减弱了FSH诱导的这些分子的表达。用小干扰RNA敲除Sp1后，血管内皮生长因子、COX2和Survivin的表达增强也被取消。综上所述，这些结果表明，FSH刺激卵巢癌细胞VEGF、COX2和Survivin的表达涉及microRNA-27A：ZBTB10特异性蛋白通路。
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.