超声-微泡介导的microRNA-449a通过调节Notch1对肺癌细胞的生长抑制作用

Ultrasound-microbubbles mediated microRNA-449a inhibits lung cancer cell growth via the regulation of Notch1

目的:基因加载的微泡(MBs)与超声结合可以提高递送效率,是一种较好的基因传递方法。本实验旨在研究超声-微泡介导的microRNA(miR)-449a通过靶向Notch1对肺癌细胞的影响。方法:检测miR-449a在肺癌组织,癌旁组织,肺癌细胞系和肺上皮细胞中的表达,并分析其与肺癌患者临床特征的关系。进行功能研究以探测miR-449a和超声-微泡介导的miR-449a在肺癌中的作用。应用RT-qPCR、Western blot分析来验证miR-449a,Notch1,增殖和凋亡相关蛋白的水平。结果:在肺癌中观察到miR-449a表达下降。miR-449a的过表达抑制了肺癌细胞增殖,促进了G2/M期阻滞和细胞凋亡。超声-微泡介导的miR-449a增强了miR-449a对细胞生长和抗凋亡的抑制作用。miR-449a通过靶向Notch1抑制肺癌细胞活性。结论:miR-449a过表达抑制肺癌细胞生长,超声-微泡介导的miR-449a增强了miR-449a对肺癌的抑制作用。该研究可能为肺癌治疗提供新的方向。

AIM:The application of gene-loaded microbubbles(MBs)combined with ultrasound that results in increased delivery efficiency,may be an excellent method of gene delivery.This study aimed to discuss effects of ultrasound-MB mediated microRNA(miR)-449a on lung cancer(LC)development by targeting Notch1.METHODS:Initially,miR-449a expression in LC tissues,paracancerous tissues,LC cell lines and lung epithelial cells was detected and its association with LC patients'clinical characteristics was analyzed.The gain-of function studies were performed to probe the roles of miR-449a and ultrasound-MB mediated miR-449a in LC progression.Then RT-qPCR combined with Western blot analysis was applied to verify the levels of miR-449a,Notch1,proliferation-and apoptosis-related proteins.RESULTS:Poorly expressed miR-449a was observed in LC.Overexpression of miR-449a suppressed LC cell proliferation,promoted G2/M arrest and apoptosis.Ultrasound-MB-mediated miR-449a strengthened inhibitory effects of miR-449a on cell growth and resistance to apoptosis.miR-449a inhibited H1299 cell activity by targeting Notch1.CONCLUSION:Our data supported that miR-449a overexpression inhibited LC cell growth,and ultrasound-MB-mediated miR-449a reinforced the repressive effects of miR-449a on LC progression.This investigation may offer new insight for LC treatment.