Effect of HIF-2α on regulating CDCP1 to promote hepatocellular carcinoma metastasis
10.3760/cma.j.issn.0253-3766.2017.01.004
- VernacularTitle: 缺氧诱导因子2α对含CUB结构域蛋白1的调控及在肝癌转移中的作用
- Author:
Manqing CAO
1
;
Junrong GAO
1
;
Jiafei HUANG
1
;
Abin YOU
1
;
Zhigui GUO
1
;
Hongyuan ZHOU
1
;
Feng FANG
1
;
Wei ZHANG
1
;
Xiaolin ZHU
1
;
Ti ZHANG
1
Author Information
1. Department of Hepatobiliary Surgery, Cancer Institute and Hospital, Tianjin Medical University, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China
- Publication Type:Journal Article
- Keywords:
Carcinoma, hepatocellular;
Neoplasm metastasis;
Hypoxia inducible factor 2α;
CUB domain-containing protein 1
- From:
Chinese Journal of Oncology
2017;39(1):18-23
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of hypoxia inducible factor 2α (HIF-2α) on regulating CUB domain-containing protein 1 (CDCP1) and its role in hepatocellular carcinoma metastasis.
Methods:HIF-2α-knocked down and HIF-2α-stably overexpressing cells (MHCC97H) were prepared by small interfering RNA (siRNA) and lentivirus transfection, respectively. The expression of CDCP1 protein and mRNA in the above cells was detected by western blot and real-time PCR. The effect of HIF-2α on cell invasion ability was determined by Transwell assay. Furthermore, immunohistochemical staining was performed to detect the expression of CDCP1 in human HCC tissue samples.
Results:Both HIF-2α and CDCP1 were induced under hypoxic conditions. The activation of CDCP1 under hypoxic conditions was dependent on the expression of HIF-2α.When HIF-2α was overexpressed, the mRNA level of CDCP1 was greatly upregulated (5.92±0.28, P<0.05). When HIF-2α was knocked down by siRNA for 48 h and 72 h, the expression of CDCP1 was significantly downregulated (48 h: 0.25±0.04; 72 h: 0.18±0.02, all P<0.05). Moreover, analysis of human HCC samples showed that CDCP1 expression was correlated with tumor-free survival (P<0.05).
Conclusions:The results of this study indicate that the expression of CDCP1 is regulated by HIF-2α and is correlated with the progression of HCC. Inhibition of HIF-2α/CDCP1 may play certain inhibitory role in the metastasis of HCC.
