• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Theranostics >A low microRNA-630 expression confers resistance to tyrosine kinase inhibitors in EGFR-mutated lung adenocarcinomas via miR-630/YAP1/ERK feedback loop
【2h】

A low microRNA-630 expression confers resistance to tyrosine kinase inhibitors in EGFR-mutated lung adenocarcinomas via miR-630/YAP1/ERK feedback loop

机译：microRNA-630的低表达通过miR-630 / YAP1 / ERK反馈环赋予对EGFR突变的肺腺癌中酪氨酸激酶抑制剂的抗性

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

>Purpose: MicroRNA-630 plays dual roles in apoptosis and drug resistance in human cancers. However, the role of miR-630 in resistance to tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma remains to be elucidated.>Methods: Manipulation of miR-630 and its targeted gene YAP1 and/or combination of inhibitor treatments was performed to explore whether low miR-630 could confer TKI resistance due to de-targeting YAP1, and this could decrease proapoptotic protein Bad expression through the miR-630/YAP1/ERK feedback loop. A retrospective study was conducted to examine whether the expression of miR-630 and YAP1 could be associated with TKI therapeutic response in patients with lung adenocarcinoma.>Results: Low miR-630 expression may confer TKI resistance via increased SP1 binding to the miR-630 promoter due to ERK activation by YAP1 de-targeting. Persistent activation of ERK signaling via the miR-630/YAP1/ERK feedback loop may be responsible for TKI resistance in EGFR-mutated cells. Moreover, a decrease in Bad expression by its phosphorylation at Serine 75 through ERK activation conferred low miR-630-mediated TKI resistance by modulating the apoptotic pathway. Xenographic tumors induced by miR-630-knockdown PC9 and PC9GR cells in nude mice were nearly suppressed by the combination of gefitinib with the YAP1 inhibitor verteporfin or an MEK/ERK inhibitor AZD6244. Patients with low miR-630 and high YAP1 expressing tumors had a higher prevalence of unfavorable responses to TKI therapy and poorer outcomes when compared with their counterparts.>Conclusion: MiR-630 may be a potential biomarker for the prediction of TKI therapeutic response and outcome in patients with lung adenocarcinoma.
机译：>目的：MicroRNA-630在人类癌症的凋亡和耐药性中起着双重作用。但是，miR-630在肺腺癌中对酪氨酸激酶抑制剂（TKIs）耐药的作用仍有待阐明。>方法：操纵miR-630及其靶向基因YAP1和/或抑制剂的组合进行了多种处理，以探讨低水平的miR-630是否会因脱靶YAP1而赋予TKI抗药性，并可能通过miR-630 / YAP1 / ERK反馈环降低促凋亡蛋白Bad表达。进行了一项回顾性研究，以探讨miR-630和YAP1的表达是否与肺腺癌患者的TKI治疗反应有关。>结果：低miR-630的表达可能通过增加SP1来赋予TKI耐药性由于通过YAP1脱靶激活ERK而与miR-630启动子结合。通过miR-630 / YAP1 / ERK反馈回路持久激活ERK信号可能是EGFR突变细胞中TKI耐药的原因。此外，通过ERK激活在丝氨酸75处的磷酸化引起的Bad表达降低，通过调节细胞凋亡途径使miR-630介导的TKI耐药性降低。吉非替尼与YAP1抑制剂verteporfin或MEK / ERK抑制剂AZD6244的组合几乎抑制了miR-630抑制PC9和PC9GR细胞在裸鼠中诱发的Xenographic肿瘤。低miR-630和高YAP1表达肿瘤的患者与同龄人相比，对TKI治疗的不良反应发生率更高，并且预后较差。>结论： MiR-630可能是预测的潜在生物标志物肺腺癌患者的TKI治疗反应和预后

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号