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Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer
Joint Authors
Felisbino, Sérgio Luis
Barquilha, Caroline N.
Santos, Nilton J.
Monção, Caio C. D.
Barbosa, Isabela C.
Lima, Flávio O.
Justulin, Luis A.
Pértega-Gomes, Nelma
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-01-20
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
The incidence of prostate cancer (PCa) is increasing, and it is currently the second most frequent cause of death by cancer in men.
Despite advancements in cancer therapies, new therapeutic approaches are still needed for treatment-refractory advanced metastatic PCa.
Cross-species analysis presents a robust strategy for the discovery of new potential therapeutic targets.
This strategy involves the integration of genomic data from genetically engineered mouse models (GEMMs) and human PCa datasets.
Considering the role of antioxidant pathways in tumor initiation and progression, we searched oxidative stress-related genes for a potential therapeutic target for PCa.
First, we analyzed RNA-sequencing data from Pb-Cre4; Ptenf/f mice and discovered an increase in sulfiredoxin (Srxn1) mRNA expression in high-grade prostatic intraepithelial neoplasia (PIN), well-differentiated adenocarcinoma (medium-stage tumors), and poor-differentiated adenocarcinoma (advanced-stage prostate tumors).
The increase of SRXN1 protein expression was confirmed by immunohistochemistry in mouse prostate tumor paraffin samples.
Analyses of human databases and prostate tissue microarrays demonstrated that SRXN1 is overexpressed in a subset of high-grade prostate tumors and correlates with aggressive PCa with worse prognosis and decreased survival.
Analyses in vitro showed that SRXN1 expression is also higher in most PCa cell lines compared to normal cell lines.
Furthermore, siRNA-mediated downregulation of SRXN1 led to decreased viability of PCa cells LNCaP.
In conclusion, we identified the antioxidant enzyme SRXN1 as a potential therapeutic target for PCa.
Our results suggest that the use of specific SRXN1 inhibitors may be an effective strategy for the adjuvant treatment of castration-resistant PCa with SRXN1 overexpression.
American Psychological Association (APA)
Barquilha, Caroline N.& Santos, Nilton J.& Monção, Caio C. D.& Barbosa, Isabela C.& Lima, Flávio O.& Justulin, Luis A.…[et al.]. 2020. Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1203888
Modern Language Association (MLA)
Barquilha, Caroline N.…[et al.]. Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-12.
https://search.emarefa.net/detail/BIM-1203888
American Medical Association (AMA)
Barquilha, Caroline N.& Santos, Nilton J.& Monção, Caio C. D.& Barbosa, Isabela C.& Lima, Flávio O.& Justulin, Luis A.…[et al.]. Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1203888
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203888