Pang Linrong, Lu Jinger, Huang Jia, Xu Caihong, Li Hui, Yuan Guangbo, Cheng Xiaochun, Chen Jun
Department of Chemoradiotherapy Center, Yinzhou People's Hospital, Ningbo, Zhejiang 315040, P.R. China.
Department of Endocrinology, Yinzhou People's Hospital, Ningbo, Zhejiang 315040, P.R. China.
Oncol Lett. 2017 Dec;14(6):7745-7752. doi: 10.3892/ol.2017.7242. Epub 2017 Oct 20.
The aim of the present study was to investigate the effects of microRNA (miR-)146a on the cisplatin sensitivity of the non-small cell lung cancer (NSCLC) A549 cell line and study the underlying molecular mechanism. The differences in expression of miRNAs between A549 and A549/cisplatin (A549/DDP) cells were determined, and miR-146a was selected to study its effect on cisplatin sensitivity of A549/DDP cells. miR-146a mimic and inhibitor transient transfection systems were constructed using vectors, and A549/DDP cells were infected with miR-146a mimic and inhibitor to investigate growth, apoptosis and migration. The directed target of miR-146a was determined and the underlying molecular mechanism was validated in the present study. The results of the present study demonstrated that miR-146a was downregulated in NSCLC A549/DDP cells, compared with A549 cells. The overexpression of miR-146a induced apoptosis and inhibited the growth and invasion of A549/DDP cells, which resulted in increased cisplatin sensitivity in NSCLC cells. The JNK2 gene was determined as the direct target of miR-146a, and may be activated by the overexpression of miR-146a. Additionally, JNK2 activated the expression of p53 and inhibited B cell lymphoma 2. The upregulation of miR-146a increased cisplatin sensitivity of the A549 cell line by targeting JNK2, which may provide a novel method for treating NSCLC cisplatin resistance.
本研究的目的是探讨微小RNA（miR-）146a对非小细胞肺癌（NSCLC）A549细胞系顺铂敏感性的影响，并研究其潜在的分子机制。测定A549细胞与A549/顺铂（A549/DDP）细胞中微小RNA表达的差异，选择miR-146a研究其对A549/DDP细胞顺铂敏感性的影响。使用载体构建miR-146a模拟物和抑制剂瞬时转染系统，用miR-146a模拟物和抑制剂感染A549/DDP细胞，以研究其生长、凋亡和迁移情况。在本研究中确定了miR-146a的直接靶点并验证了潜在的分子机制。本研究结果表明，与A549细胞相比，NSCLC A549/DDP细胞中miR-146a表达下调。miR-146a的过表达诱导A549/DDP细胞凋亡并抑制其生长和侵袭，从而导致NSCLC细胞对顺铂的敏感性增加。JNK2基因被确定为miR-146a的直接靶点，可能被miR-146a的过表达激活。此外，JNK2激活p53的表达并抑制B细胞淋巴瘤2。miR-146a的上调通过靶向JNK2增加了A549细胞系对顺铂的敏感性，这可能为治疗NSCLC顺铂耐药提供一种新方法。
