PMID- 31928714
OWN - NLM
STAT- MEDLINE
DCOM- 20200915
LR  - 20200915
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 523
IP  - 2
DP  - 2020 Mar 5
TI  - VHL enhances 9-cis-retinoic acid treatment by down-regulating retinoid X receptor 
      alpha in renal cell carcinomas.
PG  - 535-541
LID - S0006-291X(20)30068-1 [pii]
LID - 10.1016/j.bbrc.2019.12.112 [doi]
AB  - Renal cell carcinoma (RCC) is the most common malignant kidney tumors in adults. 
      Von Hippel-Lindau (VHL) gene is deficient in >50% of RCC cases, but the role of 
      VHL as a potential therapeutic target in RCC has not been well established. In 
      the present study, 9-cis-Retinoic acid, which is a potent natural agonist of 
      retinoid X receptors (RXRs), was found to decrease the viability of 
      VHL-proficient RCC cells, but had little effect on VHL-deficient RCC cells. In 
      addition, it was demonstrated that VHL transcriptionally regulated RXRalpha in a 
      hypoxia-inducible factor-alpha independent manner. Moreover, a negative correlation 
      was observed between the expressions of VHL and RXRalpha in RCC tissues. 
      Collectively, these data indicate that VHL-proficient RCC patients may be more 
      sensitive to treatment with 9-cis-retinoic acid, which acts by regulating RXRalpha 
      expression, compared with VHL-deficient RCC patients. The findings of the present 
      study demonstrate a novel function of VHL and highlight the potential of VHL 
      expression as a therapeutic modality for the optimized treatment of RCC patients.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Wang, Fen
AU  - Wang F
AD  - Department of Anesthesiology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, 200072, PR China; Department of Urology, Shanghai 
      Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, 
      PR China.
FAU - Wang, Long-Sheng
AU  - Wang LS
AD  - Department of Urology, Shanghai Tenth People's Hospital, Tongji University School 
      of Medicine, Shanghai, 200072, PR China.
FAU - Gao, Yao-Hui
AU  - Gao YH
AD  - Department of Pathology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, 200072, PR China. Electronic address: 
      gaoyaohui187@163.com.
FAU - Yao, Xu-Dong
AU  - Yao XD
AD  - Department of Urology, Shanghai Tenth People's Hospital, Tongji University School 
      of Medicine, Shanghai, 200072, PR China. Electronic address: 
      yaoxudong67@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200110
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (RXRA protein, human)
RN  - 0 (Retinoid X Receptor alpha)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - EC 2.3.2.27 (Von Hippel-Lindau Tumor Suppressor Protein)
RN  - EC 6.3.2.- (VHL protein, human)
SB  - IM
MH  - Alitretinoin/*pharmacology
MH  - Antineoplastic Agents/pharmacology
MH  - Basic Helix-Loop-Helix Transcription Factors/metabolism
MH  - Carcinoma, Renal Cell/*drug therapy
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Kidney Neoplasms/*drug therapy
MH  - Retinoid X Receptor alpha/agonists/genetics/*metabolism
MH  - Von Hippel-Lindau Tumor Suppressor Protein/genetics/*metabolism
OTO - NOTNLM
OT  - 9-cis-Retinoic acid
OT  - Renal cell carcinomas
OT  - Retinoid X receptor alpha
OT  - Von Hippel-Lindau
COIS- Declaration of competing interest The authors declare that there are no conflicts 
      of interest.
EDAT- 2020/01/14 06:00
MHDA- 2020/09/17 06:00
CRDT- 2020/01/14 06:00
PHST- 2019/12/18 00:00 [received]
PHST- 2019/12/22 00:00 [revised]
PHST- 2019/12/24 00:00 [accepted]
PHST- 2020/01/14 06:00 [pubmed]
PHST- 2020/09/17 06:00 [medline]
PHST- 2020/01/14 06:00 [entrez]
AID - S0006-291X(20)30068-1 [pii]
AID - 10.1016/j.bbrc.2019.12.112 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2020 Mar 5;523(2):535-541. doi: 
      10.1016/j.bbrc.2019.12.112. Epub 2020 Jan 10.