Up-Regulation of MiR-452 Inhibits Metastasis of Non-Small Cell Lung Cancer by Regulating BMI1
Up-Regulation of MiR-452 Inhibits Metastasis of Non-Small Cell Lung Cancer by Regulating BMI1
复制标题
DOI：
10.1159/000430362
复制
发表时间：
2015-01-01
影响因子：
--
通讯作者：
Chen, Yijiang
中科院分区：
文献类型：
--
作者：
He, Zhicheng;Xia, Yang;Chen, Yijiang
背景/目的：microRNAs(MiRNAs)已被认为是非小细胞肺癌(NSCLC)细胞过程中的一类新的调节因子。然而，miR-452与非小细胞肺癌发生发展的关系尚不清楚。方法：采用定量逆转录聚合酶链式反应(QRT-PCR)检测60例非小细胞肺癌组织中miR-452及其靶基因的表达。用Transwell法检测细胞侵袭能力。通过荧光素酶报告实验和免疫印迹实验证实了其调控机制。结果：在本研究中，相对较低的miR-452和较高的BMI1表达水平与晚期肿瘤分期和更多的淋巴结转移有关。在体外，下调miR-452可以增强细胞的侵袭能力。此外，miR-452通过与其3‘-非编码区结合来调控BMI1的表达。下调miR-452对细胞侵袭能力的增强作用可被BMI1抑制所消除。结论：miR-452在非小细胞肺癌的发生发展中起重要作用，miR-452-BMI1通路可能为非小细胞肺癌的治疗提供新的思路。版权所有(C)2015年S.Karger AG，巴塞尔
Background/Aims: MicroRNAs (miRNAs) have been regarded as a new class of regulators in cellular processes in non-small cell lung cancer (NSCLC). However, the relationship between miR-452 and the development of NSCLC remains unclear. Methods: qRT-PCR was used to detect the expression of miR-452 and its target gene in NSCLC samples (n=60). The transwell assay was used to test the cell invasion capability. The regulation mechanism was confirmed by luciferase reporter assay and western blot assay. Results: In the current study, a relatively lower miR-452 and higher BMI1 expression levels were confirmed to be associated with advanced tumor stage and more extent of lymph nodes metastasis. In vitro, down-regulated miR-452 could enhance cell invasion capability. Furthermore, miR-452 modulated BMI1 expression by binding to its 3'-UTR. The enhancement of cell invasion capability induced by down-regulated miR-452 was eliminated by repression of BMI1. Conclusions: Our results suggest that miR-452 plays a vital role in development of NSCLC, and this miR-452-BMI1 pathway might generate a novel insight into the treatment of NSCLC. Copyright (C) 2015 S. Karger AG, Basel