Clinical significance of miR-138 in patients with malignant melanoma through targeting of PDK1 in the PI3K/AKT autophagy signaling pathway
Clinical significance of miR-138 in patients with malignant melanoma through targeting of PDK1 in the PI3K/AKT autophagy signaling pathway
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DOI：
10.3892/or.2017.5838
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发表时间：
2017-09-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Zhiyu
中科院分区：
文献类型：
--
作者：
Meng, Fanjun;Zhang, Yuxia;Wang, Zhiyu
本研究调查了miR-138在恶性黑色素瘤（MM）患者中的临床意义，MM以前与肿瘤生长相关。在MM患者中，我们发现与健康对照受试者相比，miR-138的表达显著下调。与阴性对照组相比，miR-138在人黑素瘤细胞系A2058中的过表达抑制细胞增殖并诱导细胞凋亡，并且增加caspase-3和Bax蛋白表达。同时，miR-138过表达促进A2058细胞自噬，诱导LC 3蛋白表达，抑制PI 3 K/AKT/mTOR信号通路和PDK 1蛋白表达。PI 3 K抑制剂LY 294002可抑制PI 3 K/AKT/mTOR信号传导，诱导细胞凋亡，抑制细胞增殖，增加miR-138过表达后A2058细胞中caspase-3和Bax蛋白表达，降低PDK 1蛋白表达。总的来说，我们的研究结果表明，miR-138通过靶向PI 3 K/AKT/mTOR自噬信号通路中的PDK 1表达在MM患者中具有临床意义。
The present study investigated the clinical significance of miR-138 in patients with malignant melanoma ( MM), which has previously been associated with tumor growth. In patients with MM, we found that the expression of miR-138 was significantly downregulated when compared with healthy control subjects. Overexpression of miR-138 in the human melanoma cell line A2058 inhibited cell proliferation and induced cell apoptosis, and increased caspase-3 and Bax protein expression when compared with a negative control group. Meanwhile, miR-138 overexpression promoted cell autophagy, induced LC3 protein expression, and suppressed the PI3K/AKT/mTOR signaling pathway and PDK1 protein expression in A2058 cells. LY294002, an inhibitor of PI3K, suppressed PI3K/AKT/mTOR signaling, induced apoptosis, inhibited cell proliferation, increased caspase-3 and Bax protein expression, and decreased PDK1 protein expression in A2058 cells following miR-138 overexpression. Collectively, our findings indicate the clinical significance of miR-138 in patients with MM through its targeting of PDK1 expression in the PI3K/AKT/mTOR autophagy signaling pathway.