Chen Ruilin, Zhang Yongqing, Zhang Chengcheng, Wu Hua, Yang Shumei
Department of Respiratory Medicine, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
Oncol Lett. 2017 May;13(5):3905-3911. doi: 10.3892/ol.2017.5904. Epub 2017 Mar 24.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The results of the present study demonstrate that high expression of microRNA (miR)-137 and low expression of steroid receptor coactivator-3 (SRC3) had a significant negative correlation in 40 NSCLC tissue samples. In addition, cell colony formation and proliferation was significantly reduced in miR-137-transfected A549 and NCI-H838 cells compared with scramble-transfected NSCLC cell lines. miR-137 was identified to induce G/S cell cycle arrest and dysregulate the mRNA expression of cell cycle-associated proteins (proliferating cell nuclear antigen, cyclin E, cyclin A1, cyclin A2 and p21) in NSCLC cells. Notably, miR-137 could significantly suppress SRC3 3' untranslated region (UTR) luciferase-reporter activity, an effect that was not detectable when the putative 3'-UTR target-site was mutated, further clarifying the molecular mechanisms underlying the role of miR-137 in NSCLC. In conclusion, the results of the present study suggest that miR-137 suppresses NSCLC cell proliferation by partially targeting SRC3.
非小细胞肺癌(NSCLC)是最常见的肺癌类型。本研究结果表明,在40例NSCLC组织样本中,微小RNA(miR)-137的高表达与类固醇受体辅激活因子3(SRC3)的低表达呈显著负相关。此外,与乱序转染的NSCLC细胞系相比,miR-137转染的A549和NCI-H838细胞的细胞集落形成和增殖明显减少。已确定miR-137可诱导NSCLC细胞发生G/S期细胞周期阻滞并使细胞周期相关蛋白(增殖细胞核抗原、细胞周期蛋白E、细胞周期蛋白A1、细胞周期蛋白A2和p21)的mRNA表达失调。值得注意的是,miR-137可显著抑制SRC3 3'非翻译区(UTR)荧光素酶报告基因活性,当假定的3'-UTR靶位点发生突变时,这种效应无法检测到,这进一步阐明了miR-137在NSCLC中作用的分子机制。总之,本研究结果表明,miR-137通过部分靶向SRC3抑制NSCLC细胞增殖。