miRNA-200a调控FOXC1增敏肺癌EGFR-TKI治疗的研究
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科技部国际科技合作专项(2014DFA31940);国家自然科学基金(81572259);江苏省干部保健课题(BJ15018)


MiRNA-200a sensitizes non-small-cell lung cancer to EGFR-TKIs by targeting FOXC1
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    摘要:

    目的:探究miRNA-200a对非小细胞肺癌(non-small cell lung cancer, NSCLC)靶向治疗疗效的影响及其调控机制。方法:通过RT-PCR、Western blot等方法检测NSCLC细胞中miRNA-200a、FOXC1的表达量;四甲基偶氮唑盐(MTT)实验、细胞划痕实验、Transwell实验分别检测miRNA-200a、FOXC1对肺腺癌细胞生长、迁移、侵袭等生物学行为的影响;荧光素酶报告实验分析FOXC1与miRNA-200a的靶向关系。结果:高表达miRNA-200a抑制肺腺癌细胞的生长、上皮间质转化、迁移、侵袭,并且增加肺腺癌细胞对吉非替尼的敏感性。此外,敲低FOXC1同样可以抑制细胞生长,恢复肺腺癌细胞对吉非替尼敏感性。结论:上调miRNA-200a或下调FOXC1可以增强NSCLC细胞对吉非替尼的敏感性。为克服表皮生长因子受体酪氨酸激酶抑制剂治疗的耐药性提供了一种新的有效治疗方法。

    Abstract:

    Objective: To investigate the role of miRNA-200a in the efficacy of targeted therapy in non-small-cell lung cancer (NSCLC) patients and its underlying mechanisms. Methods: Real-time polymerase chain reaction and Western blot were used to investigate the level of miRNA-200a and FOXC1. The MTT assay,wound-healing and Transwell assays were performed to measure the effect of miRNA-200a and FOXC1 on cell growth, migration, invasion and other biological behaviors. Luciferase reporter assay analyzed the relationship between FOXC1 and miRNA-200a. Results: We found that a high level of miRNA-200a inhibited NSCLC cells growth, EMT, migration and invasion and increased sensitivity to gefitinib by targeting FOXC1. Furthermore, suppression of FOXC1 also inhibits cells progression and restores gefitinib resistance. Conclusion: Upregulated miRNA-200a or knockdown of FOXC1 enhanced sensitivity to gefitinib in NSCLCs. This may provide a novel effective therapeutic approach to overcome the acquisition of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) therapy.

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尹 媛,许 伟,吴双双,李 燕,赵卫红,吴剑卿. miRNA-200a调控FOXC1增敏肺癌EGFR-TKI治疗的研究[J].南京医科大学学报(自然科学版),2017,(9):1067-1075

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  • 收稿日期:2017-04-03
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  • 在线发布日期: 2017-09-25
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