scholarly journals Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1005
Author(s):  
Emiliano Ortiz ◽  
Pablo Sanchis ◽  
Juan Bizzotto ◽  
Sofia Lage-Vickers ◽  
Estefania Labanca ◽  
...  

The inflammatory tumor microenvironment is a fertile niche accelerating prostate cancer (PCa). We have reported that heme-oxygenase (HO-1) had a strong anti-tumoral effect in PCa. We previously undertook an in-depth proteomics study to build the HO-1 interactome in PCa. In this work, we used a bioinformatics approach to address the biological significance of HO-1 interactors. Open-access PCa datasets were mined to address the clinical significance of the HO-1 interactome in human samples. HO-1 interactors were clustered into groups according to their expression profile in PCa patients. We focused on the myxovirus resistance gene (MX1) as: (1) it was significantly upregulated under HO-1 induction; (2) it was the most consistently downregulated gene in PCa vs. normal prostate; (3) its loss was associated with decreased relapse-free survival in PCa; and (4) there was a significant positive correlation between MX1 and HMOX1 in PCa patients. Further, MX1 was upregulated in response to endoplasmic reticulum stress (ERS), and this stress triggered apoptosis and autophagy in PCa cells. Strikingly, MX1 silencing reversed ERS. Altogether, we showcase MX1 as a novel HO-1 interactor and downstream target, associated with ERS in PCa and having a high impact in the clinical setting.

2020 ◽  
Author(s):  
Zhien Zhou ◽  
Meiting He ◽  
Yi Zhou ◽  
Weigang Yan ◽  
Xingcheng Wu ◽  
...  

Abstract Background: Radical prostatectomy (RP) and low-dose-rate brachytherapy (LDR) are two widely used treatment options for patients with intermediate-risk prostate cancer (IRPC). However, which one is better remains controversial. Therefore, the purpose of this study was to compare the efficacy of RP vs LDR for patients with IRPC. Methods: A retrospective analysis was performed on 361 IRPC patients who underwent treatment from January 2010 and August 2017. 160 underwent RP and 201 underwent LDR using Iodine-125. Biochemical failure for RP was defined as prostate-specific antigen (PSA) levels > 0.2 ng/ml, and for LDR as nadir PSA level + 2 ng/ml. The log-rank test compared biochemical relapse-free survival (bRFS) between the two modalities, and Cox regression identified factors associated with bRFS. Results: Median follow-up was 54 months for RP and 69 months for LDR. The 5-and 8-year bRFS rates were 70.2% and 63.1% in the RP group, and 83.2% and 68.9% in the LDR group, respectively, P=0.003. There were no significant differences in terms of clinical relapse-free survival (cRFS), cancer-specific survival (CSS) or overall survival (OS) between the two groups. Conclusion: LDR is a reasonable treatment option for IRPC patients, yielding improved bRFS and equivalent rates of cRFS, CSS and OS compared with RP.


2019 ◽  
Vol 52 (3) ◽  
pp. e12576 ◽  
Author(s):  
Fabrizio Fontana ◽  
Roberta Manuela Moretti ◽  
Michela Raimondi ◽  
Monica Marzagalli ◽  
Giangiacomo Beretta ◽  
...  

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