Androgen receptor reverses the oncometabolite R-2-hydroxyglutarate-induced prostate cancer cell invasion via suppressing the circRNA-51217/miRNA-646/TGFβ1/p-Smad2/3 signaling.
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Authors
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Xu, Hua1
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Sun, Yin2
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You, Bosen2
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Huang, Chi-Ping3
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Ye, Dingwei4
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Chang, Chawnshang5
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1
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China; George Whipple Lab for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, The Wilmot Cancer Center, University of Rochester, Rochester, NY, USA, 14646.
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(China)
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2
George Whipple Lab for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, The Wilmot Cancer Center, University of Rochester, Rochester, NY, USA, 14646.
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3
Sex Hormone Research Center and Department of Urology, China Medical University, Taichung, 404, Taiwan.
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(China)
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4
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. Electronic address: [email protected]
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(China)
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5
George Whipple Lab for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, The Wilmot Cancer Center, University of Rochester, Rochester, NY, USA, 14646; Sex Hormone Research Center and Department of Urology, China Medical University, Taichung, 404, Taiwan. Electronic address: [email protected]
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(China)
- Type
- Published Article
- Journal
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Cancer letters
- Publication Date
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Mar 01, 2020
- Volume
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472
- Pages
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151–164
- Identifiers
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DOI: 10.1016/j.canlet.2019.12.014
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PMID: 31846689
- Source
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Medline
- Keywords
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- Language
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English
- License
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Unknown
Abstract
IDH1 (Isocitrate dehydrogenase 1) mutation occurring at codon 132 (R132) in prostate cancer (PCa) is considered as a classifier for a subgroup of PCas with accumulation of oncometabolite R-2HG (R-2-hydroxyglutarate). Here we found that adding R-2HG or the mutant IDH1 R132H could promote PCa cell invasion in androgen receptor (AR)-negative PC3 cells or suppressing the AR in AR-positive C4-2 cells. Mechanism dissection revealed that R-2HG could increase circRNA-51217 expression to sponge miRNA-646, which might then lead to increase TGFβ1 expression and thus induce TGFβ1/p-Smad2/3 signaling to increase PCa cell invasion. AR can suppress this R-2HG/circRNA-51217/miRNA-646/TGFβ1/p-Smad2/3 signaling-increased PCa cell invasion via repressing TGFβ1 transcription and inhibiting circRNA-51217 expression through regulating ADAR2 expression. Preclinical studies with an in vivo xenograft mouse model also revealed that PCa cells with the IDH1 R132H mutation have more invasive metastasis. This study demonstrates that IDH1 R132H mutation with increased oncometabolite R-2HG in PCa cells may play important roles to increase PCa cell invasion. Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This record was last updated on 08/13/2020 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at
https://www.ncbi.nlm.nih.gov/pubmed/31846689
