文献类型：期刊文献

英文题名：HIF-1α binding to AEG-1 promoter induced upregulated AEG-1 expression associated with metastasis in ovarian cancer

作者：Zhao, Ting[1];Zhao, Chenyan[2];Zhou, Yanting[3];Zheng, Jing[3];Gao, Shujun[4];Lu, Yuan[1]

机构：[1]Fudan Univ, Dept Gynecol, Obstet & Gynecol Hosp, 419 Fangxie Rd, Shanghai 200011, Peoples R China;[2]Fudan Univ, Dept Pathol, Obstet & Gynecol Hosp, Shanghai, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Shanghai, Peoples R China;[4]Fudan Univ, Obstet & Gynecol Hosp, Diag & Treatment Ctr Cerv Dis, Shanghai, Peoples R China

年份：2017

卷号：6

期号：5

起止页码：1072

外文期刊名：CANCER MEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000401330300019)】；

基金：This work was supported by the Shanghai Science and Technology Commission grant 15140903000 and the Shanghai Municipal Health and Family Planning Commission grant 201540224. We thank Dr. Yan Mei for his help with manuscript preparation.

语种：英文

外文关键词：AEG-1; HIF-1 alpha; metastasis; ovarian cancer; OVCAR3 cells

摘要：Ovarian cancer with the highest mortality rate among gynecological malignancies is one of common cancers among female cancer patients. As reported in recent years, AEG-1 was associated with the occurrence, development, and metastasis of ovarian cancer, but the mechanisms remain unclear. In the current study, invasion capabilities of ovarian cancer OVCAR3 cells were measured by viral infection and transwell assay. Western blot analysis was used to evaluate the expression levels of beta-catenin, E-cadherin, MMP2, and MMP9. With qRT-PCR analysis, AEG-1 and HIF-1 gene expression were detected. We used luciferase reporter gene to measure AEG-1 promoter activity under normoxia/hypoxia in OVCAR3 cells. Our work demonstrated that AEG-1 significantly enhanced invasion capabilities of OVCAR3 cells and the expression levels of -catenin, E-cadherin, MMP2, and MMP9 associated with invasion capabilities of OVCAR3 cells were upregulated. Furthermore, hypoxia enhanced invasion capabilities of OVCAR3 cells and induced AEG-1 high gene expression, which was reversed by AEG-1 knockdown lentivirus. HIF-1 alpha expression upregulation was induced in OVCAR3 cells after hypoxia. HIF-1 alpha knockdown lentivirus induced downregulated expression of AEG-1 alpha and invasion capabilities of OVCAR3 cells were also inhibited. Wild-type AEG-1 promoter activity under hypoxic conditions was significantly higher than that AEG-1 mutation under normoxic conditions in the absence of hypoxia response. Our results suggested that HIF-1 alpha binds to AEG-1 promoter to upregulate its expression, which was correlated with metastasis in ovarian cancer by inducing the expression of MMP2 and MMP9 as well as inhibiting expression of E-cadherin and beta-catenin.