PMID- 29730257
OWN - NLM
STAT- MEDLINE
DCOM- 20190515
LR  - 20190515
IS  - 1527-9995 (Electronic)
IS  - 0090-4295 (Linking)
VI  - 123
DP  - 2019 Jan
TI  - Regulation of the Antioxidant Response by MyoD Transcriptional Coactivator in 
      Castration-resistant Prostate Cancer Cells.
PG  - 296.e9-296.e18
LID - S0090-4295(18)30397-2 [pii]
LID - 10.1016/j.urology.2018.04.028 [doi]
AB  - OBJECTIVE: To reveal the potential role of the basic helix-loop-helix myogenic 
      transcription regulator MyoD in the regulation of castration-resistant prostate 
      cancer. METHODS: Expression level of MyoD was assessed in prostate cancer tissues 
      using quantitative reverse transcription polymerase chain reaction and 
      immunohistochemistry and in experimentally induced castration-resistant LNCaP/R 
      cells using quantitative reverse transcription polymerase chain reaction and 
      immunoblotting. Effect of MyoD knockdown on LNCaP/R cell progression was 
      determined by assessing cell proliferation, apoptosis, and colony formation rate. 
      The effect of MyoD knockdown on the oxidative stress state in PC3 cells was 
      determined by assessing antioxidant response gene expression and glutathione 
      synthetase-to-glutathione ratio. Finally, the functional link between the nuclear 
      factor erythroid-derived 2-related factor 1 (NRF1) and the regulation of 
      antioxidant response element-driven transcription by MyoD was studied at both 
      molecular and functional levels. RESULTS: MyoD expression was significantly 
      upregulated in hormone-refractory prostate cancer tissues and in experimentally 
      induced castration-resistant LNCaP/R cells, and MyoD knockdown effectively 
      impaired LNCaP/R cell proliferation and promoted apoptosis under 
      androgen-depleted condition. Moreover, MyoD enhanced the glutathione production 
      and protected against oxidative stress by positively regulating a cluster of 
      antioxidant genes known to be the downstream targets of NRF1. Mechanistically, 
      MyoD could augment the antioxidant response element-driven transcription in an 
      NRF1-dependent manner, and the stimulatory effect of MyoD on the antioxidant 
      response was substantially compromised in the presence of NRF1 small interfering 
      RNA treatment. CONCLUSION: We have identified an unexpected collaboration between 
      MyoD and NRF1 under androgen-depleted condition, which may serve as an important 
      adaptive mechanism during the pathogenesis of castration-resistant prostate 
      cancer.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Zhang, Shun
AU  - Zhang S
AD  - Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu 
      Hospital, Fourth Military Medical University, Xi'an, China.
FAU - Li, Lin-Hu
AU  - Li LH
AD  - Department of Urology, Jingyang County Hospital, Xianyang, China.
FAU - Qiao, Hong-Mei
AU  - Qiao HM
AD  - Department of Oncology, Baoji Affiliated Hospital of Xi'an Medical University, 
      Baoji, China.
FAU - Yang, Xue
AU  - Yang X
AD  - Department of Oncology, Baoji Affiliated Hospital of Xi'an Medical University, 
      Baoji, China.
FAU - Chen, Liang
AU  - Chen L
AD  - Department of Oncology, Baoji Affiliated Hospital of Xi'an Medical University, 
      Baoji, China.
FAU - Luo, Xiao-Hui
AU  - Luo XH
AD  - Department of Urology, Baoji Central Hospital, Baoji, China. Electronic address: 
      luoxiaohuidoctor@163.com.
LA  - eng
PT  - Journal Article
DEP - 20180503
PL  - United States
TA  - Urology
JT  - Urology
JID - 0366151
RN  - 0 (Antioxidants)
RN  - 0 (MyoD Protein)
RN  - 0 (MyoD1 myogenic differentiation protein)
SB  - IM
MH  - Antioxidants
MH  - Cell Proliferation
MH  - Humans
MH  - Male
MH  - MyoD Protein/biosynthesis/*physiology
MH  - Prostatic Neoplasms, Castration-Resistant/*etiology/metabolism/pathology
MH  - Tumor Cells, Cultured
EDAT- 2018/05/08 06:00
MHDA- 2019/05/16 06:00
CRDT- 2018/05/07 06:00
PHST- 2017/09/12 00:00 [received]
PHST- 2018/03/26 00:00 [revised]
PHST- 2018/04/25 00:00 [accepted]
PHST- 2018/05/08 06:00 [pubmed]
PHST- 2019/05/16 06:00 [medline]
PHST- 2018/05/07 06:00 [entrez]
AID - S0090-4295(18)30397-2 [pii]
AID - 10.1016/j.urology.2018.04.028 [doi]
PST - ppublish
SO  - Urology. 2019 Jan;123:296.e9-296.e18. doi: 10.1016/j.urology.2018.04.028. Epub 
      2018 May 3.