OncoTargets and Therapy (Sep 2019)
Ultrasound-microbubbles-mediated microRNA-449a inhibits lung cancer cell growth via the regulation of Notch1
Abstract
Lingwu Meng,1 Shaofei Yuan,2 Linjia Zhu,2 Zongxiao ShangGuan,2 Renguo Zhao2 1Department of Minimally Invasive Therapy, First People’s Hospital of Shangqiu, Shangqiu 476100, People’s Republic of China; 2Department of Thoracic Oncology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang Province 325200, People’s Republic of ChinaCorrespondence: Linjia ZhuDepartment of Thoracic Oncology, The Third Affiliated Hospital of Wenzhou Medical University, No. 108 Wansong Road, Ruian, Zhejiang Province 325200, People’s Republic of ChinaTel +86 05 776 586 6340Fax +86 05 776 586 6340Email [email protected]: 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 the 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. Moreover, xenograft tumors in nude mice were also applied for in vivo experiments.Results: Poorly expressed miR-449a was observed in LC, and its expression was associated with clinical staging, differentiation and lymph node metastasis of LC patients. Overexpression of miR-449a suppressed LC cell proliferation and 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.Keywords: lung cancer, microRNA-449a, H1299, ultrasound-mediated microbubbles, Notch1
