He Zhicheng, Xia Yang, Pan Chunfeng, Ma Teng, Liu Bin, Wang Juejin, Chen Liang, Chen Yijiang
Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
Cell Physiol Biochem. 2015;37(1):387-98. doi: 10.1159/000430362. Epub 2015 Aug 27.
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.
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.
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.
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.
背景/目的：微小RNA（miRNA）被认为是非小细胞肺癌（NSCLC）细胞过程中的一类新型调节因子。然而，miR-452与NSCLC发生发展之间的关系仍不清楚。
采用qRT-PCR检测60例NSCLC样本中miR-452及其靶基因的表达。采用Transwell实验检测细胞侵袭能力。通过荧光素酶报告基因实验和蛋白质免疫印迹实验证实调控机制。
在本研究中，证实相对较低的miR-452表达水平和较高的BMI1表达水平与肿瘤晚期和更多的淋巴结转移相关。在体外，下调miR-452可增强细胞侵袭能力。此外，miR-452通过结合BMI1的3'-UTR调控其表达。通过抑制BMI1消除了下调miR-452诱导的细胞侵袭能力增强。
我们的结果表明，miR-452在NSCLC发生发展中起重要作用，并且这种miR-452-BMI1途径可能为NSCLC的治疗提供新的思路。
