Back to Search
Start Over
Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer.
- Source :
-
Biomolecules [Biomolecules] 2020 Jul 06; Vol. 10 (7). Date of Electronic Publication: 2020 Jul 06. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Case-Control Studies
Cell Proliferation
Data Mining
Databases, Genetic
Endoplasmic Reticulum Stress
Gene Expression Regulation, Neoplastic
Heme Oxygenase-1 genetics
Humans
Male
Myxovirus Resistance Proteins genetics
PC-3 Cells
Prostatic Neoplasms genetics
Survival Analysis
Tumor Microenvironment
Computational Biology methods
Heme Oxygenase-1 metabolism
Myxovirus Resistance Proteins metabolism
Prostatic Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2218-273X
- Volume :
- 10
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Biomolecules
- Publication Type :
- Academic Journal
- Accession number :
- 32640729
- Full Text :
- https://doi.org/10.3390/biom10071005