Zhang Pengnan, Zhu Jie, Zheng Ya, Zhang Haiyan, Sun Hong, Gao Shujun
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University Shanghai 200000, China.
Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200000, China.
Am J Transl Res. 2019 Jul 15;11(7):4151-4165. eCollection 2019.
This current study explored the role of miRNA-574-3p and the related molecular mechanisms in epithelial ovarian cancer (EOC).
Tissues of ovarian cancer patients were applied to explore the correlation between miRNA-574-3p and EOC. The role of miRNA-574-3p in migration, invasion and chemoresistance of EOC cells was evaluated by overexpression and suppression of miRNA-574-3p in SKOV3 and CAOV3 cells. For the sake of exploring how miRNA-574-3p regulated tumor migration, invasion and chemoresistance of EOC cells, we detected several related molecular expressions and activities of signaling pathways.
Overexpression of epidermal growth factor receptor (EGFR) was correlated with downregulation of miR-574-3p in EOC tissues. Overexpression of miRNA-574-3p in EOC cells led to inhibition of cell migration as well as invasion, and it significantly promoted the sensitivities of EOC cells to paclitaxel and cisplatin. Molecular experiments showed miR-574-3p inhibited activation of AKT, FAK and c-Src, as well as MMP-9 expression via targeting EGFR.
Taken together, these data demonstrated that miRNA-574-3p inhibits both tumor metastasis and chemoresistance in EOC via targeting EGFR. Thus, targeting miRNA-574-3p may become a potential molecular method for EOC.
本研究探讨了miRNA-574-3p在上皮性卵巢癌(EOC)中的作用及相关分子机制。
应用卵巢癌患者组织探讨miRNA-574-3p与EOC的相关性。通过在SKOV3和CAOV3细胞中过表达和抑制miRNA-574-3p,评估其对EOC细胞迁移、侵袭和化疗耐药性的作用。为了探究miRNA-574-3p如何调节EOC细胞的肿瘤迁移、侵袭和化疗耐药性,我们检测了几种相关分子的表达及信号通路的活性。
表皮生长因子受体(EGFR)的过表达与EOC组织中miR-574-3p的下调相关。EOC细胞中miRNA-574-3p的过表达导致细胞迁移和侵袭受到抑制,并显著提高了EOC细胞对紫杉醇和顺铂的敏感性。分子实验表明,miR-574-3p通过靶向EGFR抑制AKT、FAK和c-Src的激活以及MMP-9的表达。
综上所述,这些数据表明miRNA-574-3p通过靶向EGFR抑制EOC中的肿瘤转移和化疗耐药性。因此,靶向miRNA-574-3p可能成为EOC的一种潜在分子治疗方法。