Wang Jiewen, Chen Xiaodong, Tong Maoqing
Dept of Gynecology and Obstetrics, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
Dept of Liver Disease, The Fifth Hospital of Bengbu, Bengbu, Anhui, China.
Gene. 2017 Jun 15;616:8-15. doi: 10.1016/j.gene.2017.03.024. Epub 2017 Mar 18.
Emerging evidence has demonstrated that AEG-1 (astrocyte elevated gene-1) plays a pivotal oncogenic role in tumorigenesis. However, the molecular mechanism by which AEG-1 exerts its oncogenic function is elusive in ovarian cancer. To explore the role and molecular insight on AEG-1-mediated tumorigenesis in ovarian cancer, multiple approaches are performed including MTT assay, flow cytometry for apoptosis and cell cycle assay, gene transfection, real-time RT-PCR, Western blotting, and Transwell assay. Our MTT assay showed that knockdown of AEG-1 by its siRNA significantly inhibited cell growth in ovarian cancer cells. Moreover, AEG-1 siRNA treatment induced G/G cell cycle arrest and triggered cell apoptosis in ovarian cancer cells. Notably, inhibition of AEG-1 suppressed cell migration and invasion in ovarian cancer cells. Intriguingly, we identified that knockdown of AEG-1 remarkably inhibited the activation of Akt pathway. Our results also validated that knockdown of AEG-1 inhibited the expression of MMP-2 and VEGF, which could lead to inhibition of cell migration and invasion. These data suggest that AEG-1 could be a potential therapeutic target for the treatment of ovarian cancer.
新出现的证据表明，AEG-1（星形胶质细胞上调基因-1）在肿瘤发生过程中发挥着关键的致癌作用。然而，在卵巢癌中，AEG-1发挥其致癌功能的分子机制尚不清楚。为了探究AEG-1介导的卵巢癌肿瘤发生的作用及分子机制，我们采用了多种方法，包括MTT法、凋亡和细胞周期检测的流式细胞术、基因转染、实时RT-PCR、蛋白质印迹法以及Transwell法。我们的MTT法显示，通过小干扰RNA（siRNA）敲低AEG-1可显著抑制卵巢癌细胞的生长。此外，AEG-1 siRNA处理可诱导卵巢癌细胞出现G/G细胞周期阻滞并引发细胞凋亡。值得注意的是，抑制AEG-1可抑制卵巢癌细胞的迁移和侵袭。有趣的是，我们发现敲低AEG-1可显著抑制Akt信号通路的激活。我们的结果还证实，敲低AEG-1可抑制基质金属蛋白酶-2（MMP-2）和血管内皮生长因子（VEGF）的表达，这可能导致细胞迁移和侵袭受到抑制。这些数据表明，AEG-1可能是治疗卵巢癌的一个潜在治疗靶点。
