Up-regulation of pVHL along with down-regulation of HIF-1Œ± by NDRG2 expression attenuates proliferation and invasion in renal cancer cells
Authors: Chui-gong Yu
Guo-jun Wu
Xia Li
Xi-ping Liu
Bei Liu
Ming-zhi Shen
Yi Ru
He Wang
Qin-hao Wang
Rui-xiao Li
Libo Yao
Guo-dong Wang
Tie-jun Pan
Ming Wei
Tian-shui Niu
Lei Gao
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Renal cell carcinoma; VHL; HIF-1Œ±; NDRG2; proliferation
Affiliations: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, the Fourth Military Medical University, Xi'an, China ; Department of Urology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China ; Department of Urology, Wuhan General Hospital, Guangzhou Command PLA, Wuhan, China., Department of Urology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China., Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China., Department of Cardiology, Hainan Branch of PLA General Hospital, Sanya, China., Department of Urology, Wuhan General Hospital, Guangzhou Command PLA, Wuhan, China., Department of Urology, Armed Police General Hospital, Beijing, China., Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, the Fourth Military Medical University, Xi'an, China., Department of Urology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.

Abstract:  The majority of renal cell carcinomas (RCCs) are characterized by loss of function of the tumor suppressor gene von Hippel Lindau (VHL), which acts as ubiquitin ligase for hypoxia-inducible factor-1Œ± (HIF-1Œ±). In the absence of VHL, HIF-1Œ± protein becomes stabilized and contributes to tumorigenesis. Recent data demonstrate the antitumor efficacy of VHL promoter in RCC cells. This study demonstrates that N-Myc downstream-regulated gene 2 (NDRG2) is a potential regulator of VHL. NDRG2 is involved in proliferation and invasion of cancer cell, furthermore it is frequently down-regulated in renal cell carcinoma. Herein we evaluated the effect of NDRG2 overexpression on proliferation and invasion in human renal cancer cells. The human renal cancer cell line 786-O and A498 were infected with Ad-NDRG2 or Ad-LacZ. Overexpression of NDRG2 not only inhibited the growth of the cells, but also suppressed the invasion. Further study showed that the tumor suppressor gene VHL were up-regulated, whereas transcription factor HIF-1a and vascular endothelial growth factor (VEGF) were down-regulated in 786-O cells infected by Ad-NDRG2. Finally, in a nude mouse model, intratumoral injections of Ad-NDRG2 every 3 days for a total of seven times significantly inhibited the growth and angiogenesis of xenografted 786-O tumors. In conclusion, these data indicate that NDRG2 may be involved in proliferation and invasion by impacting the expression of VHL and HIF-1Œ±. NDRG2 may be an attractive therapeutic target for renal cell carcinoma. 

Retracted: No

PubPeer comments:
 Figure 6B: A micrograph has been duplicated and presented as something else. Figure 8C: Same problem as in Figure 6B Figure 6C and 8D: Many flow cytometry dot plots are more similar than you would expect. They are not identical, but some patterns are.   ,