METHODS: The Exo was extracted from hBMSCs and added to A549 and H1299 cell culture, followed by the detection of cell proliferation, migration, and invasion. The correlation between the expression of miR-145-5p and SOX9, as well as their binding relationship was determined by correlation analysis, luciferase gene reporter assay and RNA pull-down assays. The in vivo animal model was established to further verify the impact of hBMSCs-Exo.
RESULTS: It showed that miR-145-5p was downregulated and SOX9 was upregulated in NSCLC tissues. HBMSCs-derived Exo, and hBMSCs-Exo with overexpression of miR-145-5p could inhibit cell proliferation, migration, and invasion of both A549 and H1299 cells, and prevent against tumor progression in vivo. MiR-145-5p and SOX9 were found to be able to bind to each other, and a negative correlation were observed between the expression of them in NSCLC tissues. Furthermore, inhibition of SOX9 could reversed the suppressed role of miR-145-5p in vitro and in vivo.
CONCLUSIONS: Therefore, HBMSCs-Exo effectively transmitted miR-145-5p, leading to the suppression of malignant development in NSCLC through the regulation of SOX9.
方法:从hBMSCs中提取Exo并添加到A549和H1299细胞培养物中,然后检测细胞增殖,迁移,和入侵。通过相关性分析确定miR-145-5p和SOX9的表达之间的相关性以及它们之间的结合关系。荧光素酶基因报告基因测定和RNA下拉测定。建立体内动物模型以进一步验证hBMSCs-Exo的影响。
结果:显示miR-145-5p在NSCLC组织中下调,SOX9上调。HBMSCs来源的Exo,过表达miR-145-5p的hBMSCs-Exo可抑制细胞增殖,迁移,以及A549和H1299细胞的侵袭,并防止体内肿瘤进展。发现MiR-145-5p和SOX9能够彼此结合,两者在NSCLC组织中的表达呈负相关。此外,SOX9的抑制可以在体外和体内逆转miR-145-5p的抑制作用。
结论:因此,HBMSCs-Exo有效传递miR-145-5p,通过调节SOX9抑制NSCLC的恶性发展。