微小RNA-149通过靶向RAP1B并使Wnt/β-连环蛋白信号通路失活来抑制肺腺癌的进展。
MicroRNA-149 inhibits the progression of lung adenocarcinoma through targeting RAP1B and inactivating Wnt/β-catenin pathway.
作者信息
Jiang W-S, Huang C-L, Zhang J, Xu F, Dai X-H
机构信息
Department of Respiratory Medicine, Chengyang People's Hospital, Qingdao, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 May;24(9):4846-4854. doi: 10.26355/eurrev_202005_21173.
OBJECTIVE
MicroRNAs (miRNAs) are important regulators in the progression of lung adenocarcinoma (LAD). Moreover, microRNA-149 (miR-149) exhibits different roles in human cancers. Hence, this study mainly focused on the function of miR-149 in LAD.
PATIENTS AND METHODS
Western blot analysis and Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) were used to quantify expression levels. The regulatory mechanism of miR-149/RAP1B was explored by methyl thiazolyl tetrazolium (MTT), transwell, and Dual-Luciferase reporter assays.
RESULTS
Downregulation of miR-149 was detected in LAD and predicted worse prognosis in patients with LAD. Functionally, overexpression of miR-149 inhibited cell viability and metastasis in LAD. In addition, miR-149 directly targets RAP1B and restrained its expression in LAD. Furthermore, upregulation of RAP1B attenuated the inhibitory effect of miR-149 on LAD. Besides that, miR-149 blocked epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathway in LAD.
CONCLUSIONS
MiR-149 inhibited the progression of LAD by restraining RAP1B/EMT and inactivating Wnt/β-catenin pathway.
目的
微小RNA（miRNA）是肺腺癌（LAD）进展中的重要调节因子。此外，微小RNA-149（miR-149）在人类癌症中发挥着不同作用。因此，本研究主要聚焦于miR-149在LAD中的功能。
患者与方法
采用蛋白质免疫印迹分析和实时定量聚合酶链反应（RT-qPCR）来定量表达水平。通过甲基噻唑基四氮唑（MTT）、Transwell和双荧光素酶报告基因检测来探究miR-149/RAP1B的调控机制。
结果
在LAD中检测到miR-149表达下调，且预测LAD患者预后较差。在功能上，miR-149过表达抑制LAD细胞的活力和转移。此外，miR-149直接靶向RAP1B并抑制其在LAD中的表达。此外，RAP1B上调减弱了miR-149对LAD的抑制作用。除此之外，miR-149阻断LAD中的上皮-间质转化（EMT）和Wnt/β-连环蛋白通路。
结论
miR-149通过抑制RAP1B/EMT和使Wnt/β-连环蛋白通路失活来抑制LAD的进展。
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