Xia M, Duan M-L, Tong J-H, Xu J-G
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Eur Rev Med Pharmacol Sci. 2015 Dec;19(24):4728-37.
Lung cancer, including non-small cell lung cancer (NSCLC), is the leading cause of cancer-related mortality worldwide. Despite recent advances in clinical and experimental oncology, the prognosis of patients with NSCLC still remains poor and the average survival time of patients suffer from lung cancer is low. Therefore, the potential mechanism accounting for the tumorigenesis of NSCLC is still needed to be explored.
A lentiviral vector over-expressing miR-26b in A549 lung cancer cells was constructed. Cell proliferation, migration and invasion analysis were measured by cell counting kit (MTT), would healing assay and Transwell assay. Direct target of miR-26b in A549 cells was examined using bioinformatics and Luciferase assay.
Herein, we found that over-expression of miR-26b significantly inhibited the proliferation, migration and invasion of A549 lung cancer cell in vitro and suppressed the growth of established tumors in vivo. By using bioinformatics, we found that COX-2 (Cyclooxygenase-2) is one of the potential targets of miR-26b. Moreover, miR-26b was found to negatively regulate COX-2 protein level by directly targeting its 3'UTR. In addition, depletion of endogenous COX-2 by the specific siRNA could mimic the function of miR-26b overexpression.
Taken together, our results demonstrate that miR-26b could suppress lung cancer cells proliferation, migration and invasion by directly negative regulation of COX-2. MiR-26b could serve as a novel potential marker for NSCLC therapy.
肺癌，包括非小细胞肺癌（NSCLC），是全球癌症相关死亡的主要原因。尽管临床和实验肿瘤学最近取得了进展，但NSCLC患者的预后仍然很差，肺癌患者的平均生存时间较短。因此，仍需要探索NSCLC肿瘤发生的潜在机制。
构建在A549肺癌细胞中过表达miR-26b的慢病毒载体。通过细胞计数试剂盒（MTT）、伤口愈合试验和Transwell试验测量细胞增殖、迁移和侵袭分析。使用生物信息学和荧光素酶试验检测A549细胞中miR-26b的直接靶标。
在此，我们发现miR-26b的过表达在体外显著抑制A549肺癌细胞的增殖、迁移和侵袭，并在体内抑制已建立肿瘤的生长。通过生物信息学，我们发现COX-2（环氧化酶-2）是miR-26b的潜在靶标之一。此外，发现miR-26b通过直接靶向其3'UTR负调控COX-2蛋白水平。此外，用特异性siRNA耗尽内源性COX-2可模拟miR-26b过表达的功能。
综上所述，我们的结果表明，miR-26b可通过直接负调控COX-2抑制肺癌细胞的增殖、迁移和侵袭。miR-26b可作为NSCLC治疗的一种新的潜在标志物。
