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

doi:10.12092/j.issn.1009-2501.2019.12.011

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (12): 1385-1393.doi: 10.12092/j.issn.1009-2501.2019.12.011

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

朱林佳¹，原少斐¹，上官宗校¹，慈晓¹，赵仁国¹，李玉苹²

¹温州医科大学附属第三医院，²温州医科大学附属第一医院，温州 325200，浙江

收稿日期:2019-09-19 修回日期:2019-10-18 出版日期:2019-12-26 发布日期:2020-01-07
通讯作者: 李玉苹，女，教授，主任医师，研究方向：肺癌靶向治疗。 Tel: 13868467423 E-mail: ysf1004@163.com
作者简介:朱林佳，女，在读硕士，副主任医师，研究方向：肺癌靶向治疗。 Tel: 13906871971 E-mail: kitty.linjia@163.com
基金资助:
浙江省医药卫生科技计划项目（2016101300）

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

ZHU Linjia ¹, YUAN Shaofei¹, SHANGGUAN Zongxiao ¹, CI Xiao¹, ZHAO Renguo ¹, LI Yuping ²

¹Department of Respiratory Medicine, the Third Affiliated Hospital, Wenzhou Medical University, Wenzhou 325200, Zhejiang, China；²Department of Respiratory Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325200, Zhejiang, China

Received:2019-09-19 Revised:2019-10-18 Online:2019-12-26 Published:2020-01-07

摘要/Abstract

摘要：

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。

关键词: 肺癌, 微小RNA-449a, 超声介导的微泡, Notch1

Abstract:

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.

Key words: lung cancer, microRNA-449a, ultrasound-mediated microbubbles, Notch1

中图分类号:

R734
R965.2

朱林佳，原少斐，上官宗校，慈晓，赵仁国，李玉苹. 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[J]. 中国临床药理学与治疗学, 2019, 24(12): 1385-1393.

ZHU Linjia, YUAN Shaofei, SHANGGUAN Zongxiao, CI Xiao, ZHAO Renguo, LI Yuping. Ultrasound-microbubbles mediated microRNA-449a inhibits lung cancer cell growth via the regulation of Notch1[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(12): 1385-1393.

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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

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