Meng Fanjun, Zhang Yuxia, Li Xing, Wang Juan, Wang Zhiyu
Department of Dermatology, Shangqiu First People's Hospital, Henan 476100, P.R. China.
Research Department, Shangqiu Medical College Shangqiu, Henan 476100, P.R. China.
Oncol Rep. 2017 Sep;38(3):1655-1662. doi: 10.3892/or.2017.5838. Epub 2017 Jul 19.
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.
本研究调查了miR - 138在恶性黑色素瘤（MM）患者中的临床意义，此前miR - 138已被发现与肿瘤生长有关。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。在人黑色素瘤细胞系A2058中过表达miR - 138可抑制细胞增殖并诱导细胞凋亡，与阴性对照组相比，还可增加caspase - 3和Bax蛋白表达。同时，miR - 138过表达促进细胞自噬，诱导LC3蛋白表达，并抑制A2058细胞中的PI3K/AKT/mTOR信号通路和PDK1蛋白表达。PI3K抑制剂LY294002在miR - 138过表达后，可抑制A2058细胞中的PI3K/AKT/mTOR信号传导，诱导凋亡，抑制细胞增殖，增加caspase - 3和Bax蛋白表达，并降低PDK1蛋白表达。总的来说，我们的研究结果表明，miR - 138通过靶向PI3K/AKT/mTOR自噬信号通路中的PDK1表达，在MM患者中具有临床意义。
