Zhang Yue, Peng Ge, Wang Ying, Cui Lixia, Wu Wenqing, Wang Luan, Liu Chengyu, Han Xiuping
Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China.
Clin Exp Pharmacol Physiol. 2017 Jul;44(7):815-826. doi: 10.1111/1440-1681.12767.
Melanoma is an aggressive skin malignancy with a high mortality. Astrocyte elevated gene-1 (AEG-1), a downstream target of Ras and c-Myc, has been implicated in the development of multiple tumours, but its role in melanoma remains unclear. In the present study, the role of AEG-1 in melanoma was explored through AEG-1 silencing. Our results showed that silencing AEG-1 inhibited the proliferation of melanoma cells, induced cell cycle arrest, and reduced levels of cyclin A, cyclin B, cyclin D1, cyclin E, and cyclin-dependent kinase 2. AEG-1silencing also induced apoptosis in melanoma cells and altered the levels of cleaved caspase-3, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein. Moreover, silencing AEG-1 suppressed the migration and invasion of melanoma cells, reduced the expressions and activities of matrix metallopeptidase (MMP)-2 and MMP-9, and inhibited the activation of the Wnt/β-catenin signalling pathway in melanoma cells. Furthermore, in vivo experiments revealed that AEG-1 silencing inhibited the growth of melanoma xenografts in nude mice. In summary, our study demonstrates an oncogenic role of AEG-1 in melanoma and suggests that AEG-1 may serve as a potential therapeutic target in the treatment of melanoma.
黑色素瘤是一种侵袭性皮肤恶性肿瘤，死亡率很高。星形胶质细胞上调基因1（AEG-1）是Ras和c-Myc的下游靶点，与多种肿瘤的发生发展有关，但其在黑色素瘤中的作用仍不清楚。在本研究中，通过沉默AEG-1来探讨其在黑色素瘤中的作用。我们的结果表明，沉默AEG-1可抑制黑色素瘤细胞的增殖，诱导细胞周期停滞，并降低细胞周期蛋白A、细胞周期蛋白B、细胞周期蛋白D1、细胞周期蛋白E和细胞周期蛋白依赖性激酶2的水平。沉默AEG-1还可诱导黑色素瘤细胞凋亡，并改变裂解的半胱天冬酶-3、B细胞淋巴瘤-2（Bcl-2）和Bcl-2相关X蛋白的水平。此外，沉默AEG-1可抑制黑色素瘤细胞的迁移和侵袭，降低基质金属蛋白酶（MMP）-2和MMP-9的表达及活性，并抑制黑色素瘤细胞中Wnt/β-连环蛋白信号通路的激活。此外，体内实验表明，沉默AEG-1可抑制裸鼠体内黑色素瘤异种移植瘤的生长。总之，我们的研究证明了AEG-1在黑色素瘤中的致癌作用，并表明AEG-1可能作为治疗黑色素瘤的潜在治疗靶点。
