Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Int J Oncol. 2017 Sep;51(3):812-822. doi: 10.3892/ijo.2017.4074. Epub 2017 Jul 17.
Astrocyte elevated gene-1 (AEG-1), known as an oncogene, is overexpressed in various cancers and implicated in tumor progression and metastasis. However, its functional significance and underlying molecular mechanisms in thyroid cancer remain to be elucidated. In the present study, we detected the potential function of AEG-1 in papillary thyroid cancer (PTC). We also investigated the relation between AEG-1 and matrix metalloproteases (MMP)2 and 9 through immunohistochemistry, western blotting, real-time PCR, immunofluorescence staining, zymography and co-immunoprecipitation (Co-IP). We found that overexpression of AEG-1 in PTC was positively correlated with lymph node metastasis and MMP2/9 expression. Knockdown of AEG-1 reduced the capacity of migration and invasion through downregulation of MMP2/9 in thyroid cancer cells. Furthermore, we firstly found that AEG-1 interacted with MMP9 in thyroid cancer cells. AEG-1 was associated with the activation of the nuclear factor κB (NF-κB) signaling pathways in thyroid cancer cells. Overall, our results for the first time showed that AEG-1 interacted with MMP9 in thyroid cancer cells and AEG-1 expression was closely associated with progression and metastasis of papillary thyroid cancer. AEG-1 might be a potential therapeutic target in papillary thyroid cancer.
星形细胞上调基因-1（AEG-1），作为一种癌基因，在多种癌症中过度表达，并与肿瘤的进展和转移有关。然而，其在甲状腺癌中的功能意义和潜在的分子机制仍有待阐明。在本研究中，我们检测了 AEG-1 在甲状腺乳头状癌（PTC）中的潜在功能。我们还通过免疫组织化学、蛋白质印迹、实时 PCR、免疫荧光染色、酶谱和免疫共沉淀（Co-IP）研究了 AEG-1 与基质金属蛋白酶（MMP）2 和 9 之间的关系。我们发现，AEG-1 在 PTC 中的过表达与淋巴结转移和 MMP2/9 表达呈正相关。在甲状腺癌细胞中，敲低 AEG-1 通过下调 MMP2/9 降低了迁移和侵袭的能力。此外，我们首次发现 AEG-1 在甲状腺癌细胞中与 MMP9 相互作用。AEG-1 与甲状腺癌细胞中核因子 κB（NF-κB）信号通路的激活有关。总的来说，我们的研究结果首次表明，AEG-1 在甲状腺癌细胞中与 MMP9 相互作用，AEG-1 的表达与甲状腺乳头状癌的进展和转移密切相关。AEG-1 可能是甲状腺乳头状癌的一个潜在治疗靶点。
