Zhao Xiaoming, Liu Ming, Li Daotang
Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, 250117, Shandong, People's Republic of China.
Mol Cell Biochem. 2015 Feb;400(1-2):1-7. doi: 10.1007/s11010-014-2228-7. Epub 2014 Dec 4.
Oleanolic acid (OA) is a natural compound from plants with anti-tumor activities. However, the mechanism of the inhibitory effect of OA on cell cycle progression has not been completely explored. We employed several lung carcinoma cell lines to investigate the cell cycle-related molecular pathway affected by OA. The data revealed that OA suppressed the proliferation of lung cancer cells in both dose- and time-dependent manners, along with an increase in miR-122 abundance. The suppression of miR-122 abolished the effect of OA on lung cancer cells. CCNG1 and MEF2D, two putative miR-122 targets, were found to be downregulated by OA treatment. Restoring their expression counteracted the effect of OA on lung carcinoma cells. OA was further shown to induce the expression of miR-122-regulating transcriptional factors in lung cancer cells. Collectively, OA induced cell cycle arrest in lung cancer cells through miR-122/Cyclin G1/MEF2D pathway. This finding may contribute to the understanding of the molecular mechanism of OA's anti-tumor activity.
齐墩果酸（OA）是一种具有抗肿瘤活性的植物天然化合物。然而，OA对细胞周期进程抑制作用的机制尚未完全阐明。我们采用多种肺癌细胞系来研究受OA影响的细胞周期相关分子途径。数据显示，OA以剂量和时间依赖性方式抑制肺癌细胞增殖，同时miR-122丰度增加。抑制miR-122可消除OA对肺癌细胞的作用。发现CCNG1和MEF2D这两个假定的miR-122靶标在OA处理后表达下调。恢复它们的表达可抵消OA对肺癌细胞的作用。进一步研究表明，OA可诱导肺癌细胞中miR-122调节转录因子的表达。总体而言，OA通过miR-122/细胞周期蛋白G1/MEF2D途径诱导肺癌细胞的细胞周期停滞。这一发现可能有助于理解OA抗肿瘤活性的分子机制。
