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微小RNA-545通过使Wnt/β-连环蛋白信号通路失活,靶向锌指E盒结合蛋白2以抑制非小细胞肺癌的发展。

MicroRNA-545 targets ZEB2 to inhibit the development of non-small cell lung cancer by inactivating Wnt/β-catenin pathway.

作者信息

Cui Jianying, Pan Guodong, He Qingjuan, Yin Lizhi, Guo Rui, Bi Hongmei

机构信息

Department of Respiratory Medicine, Anqiu People's Hospital, Weifang, Shandong 262100, P.R. China.

Department of Thoracic Surgery, Traditional Chinese Medical Hospital of Huangdao District, Qingdao, Shandong 266500, P.R. China.

出版信息

Oncol Lett. 2019 Sep;18(3):2931-2938. doi: 10.3892/ol.2019.10619. Epub 2019 Jul 15.

Abstract

The specific function of microRNA-545 (miR-545) has been reported to regulate the development of human cancers. However, the effect of miR-545 is still unclear in non-small cell lung cancer (NSCLC). Hence, this study explored the molecular mechanism of miR-545 in NSCLC. The expression levels of miR-545 and ZEB2 were measured through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. The protein expression was detected by western blotting. Dual luciferase assay was applied to evaluate the relationship between miR-545 and zinc finger E-box-binding homeobox 2 (ZEB2). MTT and Transwell assays were used to investigate the function of miR-545 in NSCLC. The expression of miR-545 was decreased in NSCLC tissues. The overexpression of miR-545 suppressed the migration, invasion and proliferation of NSCLC cells. Furthermore, ZEB2 was a direct target gene of miR-545. The knockout of ZEB2 suppressed the development of NSCLC. miR-545 inhibited the progression of NSCLC through targeting ZEB2. Moreover, miR-545 repressed the development of NSCLC via blocking EMT and Wnt/β-catenin pathway. In conclusion, miR-545 inhibited the progression of NSCLC through targeting ZEB2 and blocking EMT and Wnt/β-catenin pathway.

摘要

据报道,微小RNA-545(miR-545)的特定功能可调节人类癌症的发展。然而,miR-545在非小细胞肺癌(NSCLC)中的作用仍不清楚。因此,本研究探讨了miR-545在NSCLC中的分子机制。通过逆转录-定量聚合酶链反应(RT-qPCR)检测miR-545和锌指E盒结合同源框2(ZEB2)的表达水平。通过蛋白质印迹法检测蛋白质表达。应用双荧光素酶测定法评估miR-545与ZEB2之间的关系。采用MTT和Transwell测定法研究miR-545在NSCLC中的功能。NSCLC组织中miR-545的表达降低。miR-545的过表达抑制了NSCLC细胞的迁移、侵袭和增殖。此外,ZEB2是miR-545的直接靶基因。ZEB2的敲除抑制了NSCLC的发展。miR-545通过靶向ZEB2抑制NSCLC的进展。此外,miR-545通过阻断上皮-间质转化(EMT)和Wnt/β-连环蛋白信号通路抑制NSCLC的发展。总之,miR-545通过靶向ZEB2并阻断EMT和Wnt/β-连环蛋白信号通路抑制NSCLC的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc8/6676444/998d6845d604/ol-18-03-2931-g00.jpg

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