Open AccessHIF ‐1 α binding to AEG ‐1 promoter induced upregulated AEG ‐1 expression associated with metastasis in ovarian cancer
Author(s) -
Zhao Ting,
Zhao Chenyan,
Zhou Yanting,
Zheng Jing,
Gao Shujun,
Lu Yuan
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1053
Subject(s) - gene knockdown , mmp2 , downregulation and upregulation , ovarian cancer , cancer research , mmp9 , metastasis , western blot , biology , cancer , microbiology and biotechnology , cell culture , gene , genetics
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 OVCAR 3 cells were measured by viral infection and transwell assay. Western blot analysis was used to evaluate the expression levels of β ‐catenin, E‐cadherin, MMP 2, and MMP 9. With qRT ‐ PCR analysis, AEG ‐1 and HIF ‐1 α gene expression were detected. We used luciferase reporter gene to measure AEG ‐1 promoter activity under normoxia/hypoxia in OVCAR 3 cells. Our work demonstrated that AEG ‐1 significantly enhanced invasion capabilities of OVCAR 3 cells and the expression levels of β ‐catenin, E‐cadherin, MMP 2, and MMP 9 associated with invasion capabilities of OVCAR 3 cells were upregulated. Furthermore, hypoxia enhanced invasion capabilities of OVCAR 3 cells and induced AEG ‐1 high gene expression, which was reversed by AEG ‐1 knockdown lentivirus. HIF ‐1 α expression upregulation was induced in OVCAR 3 cells after hypoxia. HIF ‐1 α knockdown lentivirus induced downregulated expression of AEG ‐1 and invasion capabilities of OVCAR 3 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 α binds to AEG ‐1 promoter to upregulate its expression, which was correlated with metastasis in ovarian cancer by inducing the expression of MMP 2 and MMP 9 as well as inhibiting expression of E‐cadherin and β ‐catenin.