Bai Ming, Zhang Mingzi, Long Fei, Yu Nanze, Zeng Ang, Zhao Ru
Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, P.R. China.
Oncol Rep. 2017 May;37(5):2702-2710. doi: 10.3892/or.2017.5537. Epub 2017 Mar 30.
In the present study, we analyzed the role of microRNA-194 circulating regulated human melanoma cell growth. We found that microRNA-194 expression was markedly suppressed in human melanoma patients, compared with negative control group. Next, disease-free survival (DFS) and overall survival (OS) of high expression in human melanoma patients was higher than those of low expression in human melanoma patients. MicroRNA-194 overexpression inhibited cell proliferation, induced apoptosis, increased caspase-3/-9 activities and promoted Bax/Bcl-2 of human melanoma cells. Furthermore, microRNA-194 overexpression also suppressed PI3K/AKT/FoxO3a signaling pathway and induced p53/p21 signaling pathway. PI3K inhibitor, suppressed PI3K, phosphorylation-AKT, FoxO3a protein expression and increased the effects of microRNA-194 overexpression on cell growth, apoptosis, caspase-3/-9 activities and Bax/Bcl-2 protein expression of human melanoma cells through the induction of p53/p21 signaling pathway. Taken together, these data indicate that circulating microRNA-194 regulated human melanoma cells via PI3K/AKT/FoxO3a and p53/p21 signaling pathway.
在本研究中,我们分析了循环中的微小RNA-194对人黑色素瘤细胞生长的调节作用。我们发现,与阴性对照组相比,人黑色素瘤患者中微小RNA-194的表达明显受到抑制。接下来,人黑色素瘤患者中高表达组的无病生存期(DFS)和总生存期(OS)高于低表达组。微小RNA-194过表达抑制人黑色素瘤细胞的增殖,诱导细胞凋亡,增加半胱天冬酶-3/-9的活性,并促进Bax/Bcl-2的表达。此外,微小RNA-194过表达还抑制PI3K/AKT/FoxO3a信号通路并诱导p53/p21信号通路。PI3K抑制剂通过诱导p53/p21信号通路,抑制PI3K、磷酸化-AKT、FoxO3a蛋白表达,并增强微小RNA-194过表达对人黑色素瘤细胞生长、凋亡、半胱天冬酶-3/-9活性和Bax/Bcl-2蛋白表达的影响。综上所述,这些数据表明循环中的微小RNA-194通过PI3K/AKT/FoxO3a和p53/p21信号通路调节人黑色素瘤细胞。