The up-regulation of NDRG1 by HIF counteracts the cancer-promoting effect of HIF in VHL-deficient clear cell renal cell carcinoma

被引：17

作者：

Zhang, Zheng-Yan ^{[1
,2
]}

Zhang, Shi-Long ^{[1
,2
]}

Chen, Hui-Ling ^{[1
,2
]}

Mao, Yu-Qin ^{[1
,2
]}

Li, Zhan-Ming ^{[1
,2
]}

Kong, Chao-Yue ^{[1
,2
]}

Han, Bing ^{[1
,2
]}

Zhang, Jin ^{[3
]}

Chen, Yong-Hui ^{[3
]}

Xue, Wei ^{[3
]}

Zhai, Wei ^{[3
]}

Wang, Li-Shun ^{[1
,2
]}

机构：

[1] Fudan Univ, Minhang Hosp, Key Lab Whole Period Monitoring & Precise Interve, Shanghai 201100, Peoples R China

[2] Fudan Univ, Minhang Hosp, Inst Fudan Minhang Acad Hlth Syst, Shanghai, Peoples R China

[3] Shanghai Jiao Tong Univ, Renji Hosp, Dept Urol, Sch Med, Shanghai 201100, Peoples R China

来源：

CELL PROLIFERATION | 2020年 / 53卷 / 07期

基金：

中国国家自然科学基金;

关键词：

clear cell renal cell carcinoma; HIF-1; 2; alpha; metastasis; NDRG1; proliferation; SMALL-MOLECULE INHIBITORS; METASTASIS SUPPRESSOR NDRG1; HYPOXIA-INDUCIBLE FACTOR-1; GROWTH-FACTOR RECEPTOR; TUMOR-METASTASIS; GENE; IDENTIFICATION; EXPRESSION; DRG-1; HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA;

D O I：

10.1111/cpr.12853

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background Hypoxia-inducible factors (HIFs) are thought to play important roles in the carcinogenesis and progression of VHL-deficient clear cell renal cell carcinoma (ccRCC). Methods The roles of HIF-1/2 alpha in VHL-deficient clear cell renal cell carcinoma were evaluated by bioinformatics analysis, immunohistochemistry staining and Kaplan-Meier survival analysis. The downstream genes that counteract the cancer-promoting effect of HIF were analysed by unbiased proteomics and verified by in vitro and in vivo assays. Results There was no correlation between the high protein level of HIF-1/2 alpha and the poor prognosis of ccRCC patients in our large set of clinical data. Furthermore, NDRG1 was found to be up-regulated by both HIF-1 alpha and -2 alpha at the cellular level and in ccRCC tissues. Intriguingly, the high NDRG1 expression was correlated with lower Furman grade, TNM stage and longer survival for ccRCC patients compared with the low NDRG1 expression. In addition, NDRG1 suppressed the expression of series oncogenes as well as the proliferation, metastasis and invasion of VHL-deficient ccRCC cells in vitro and vivo. Conclusions Our study demonstrated that HIF downstream gene of NDRG1 may counteract the cancer-promoting effect of HIF. These results provided evidence that NDRG1 may be a potential prognostic biomarker as well as a therapeutic target in ccRCC.

引用

页数：17

共 49 条

[31] The metastasis suppressor NDRG1 down-regulates the epidermal growth factor receptor via a lysosomal mechanism by up-regulating mitogen-inducible gene 6 [J].