miR-200c通过靶向下调FOXC1逆转宫颈癌细胞顺铂耐药性的机制研究

miR-200c reversed cisplatin resistance of cervical cancer cells through downregulating FOXC1

目的:探讨miR-200c通过调控叉头框转录因子C1(FOXC1)影响宫颈癌细胞对顺铂敏感性的机制研究。方法:qRT-PCR法检测miR-200c在宫颈癌顺铂耐药组织和细胞中的表达水平。CCK-8和Annexin V-FITC/PI双染流式术检测过表达miR-200c对宫颈癌细胞增殖和凋亡的影响;双荧光素酶报告基因验证miR-200c与FOXC1的靶向作用关系;进一步实验,探讨miR-200c通过靶向FOXC1对HeLa/DDP细胞恶性生物学行为的影响。结果:miR-200c在宫颈癌耐药组织和HeLa/DDP细胞中均低表达。过表达miR-200c可显著抑制HeLa/DDP细胞增殖和促进细胞凋亡。双荧光素酶报告基因证实,miR-200c靶向作用FOXC1并下调其表达水平。过表达miR-200c通过靶向下调FOXC1进而显著抑制HeLa/DDP细胞增殖和诱导细胞凋亡,从而增强HeLa/DDP细胞对顺铂的敏感性。结论:miR-200c通过下调FOXC1表达增强宫颈癌HeLa/DDP细胞对顺铂的敏感性。

Objective:To investigate the effect of miR-200c on the sensitivity of cervical cancer cells to cisplatin by regulating forkhead box protein C1(FOXC1).Methods:The expression of miR-200c in cisplatin resistance of cervical cancer tissues and cell lines were performed by qRT-PCR.CCK-8 and Annexin V-FITC/PI double staining flow cytometry assay were applied to evaluate the effect of miR-200c overexpression on the proliferation and apoptosis of cervical cancer cells.The relationship between miR-200c and FOXC1 was examined by dual luciferase report gene assay.Furthermore,to investigate the effect of miR-200c on malignant biological behavior of HeLa/DDP cell via targeting FOXC1.Results:qRT-PCR revealed miR-200c low expression in gastric cancer tissues and cell lines of cisplatin resistance.Overexpression of miR-200c significantly inhibited cell proliferation and induced apoptosis of cervical cancer cells.Dual luciferase reporter gene assay result showed that FOXC1 was a direct target of miR-200c and suppressed by it.Mechanistically,overexpression of miR-200c significantly inhibited proliferation and induced apoptosis of HeLa/DDP cells by targeting down-regulation of FOXC1,thereby enhancing the sensitivity of HeLa/DDP cells to cisplatin.Conclusion:miR-200c enhanced the sensitivity of HeLa/DDP cells to cisplatin by down-regulating FOXC1.