Prognostic value of circulating mitochondrial DNA in prostate cancer and underlying mechanism.

Autor: Borah S; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, 90048 CA, USA., Mishra R; Department of Life Sciences, CSJM University, Kanpur, Uttar Pradesh 208012, India., Dey S; Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA., Suchanti S; Department of Biosciences, Manipal University Jaipur, Rajasthan 303007, India., Bhowmick NA; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, 90048 CA, USA; Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA., Giri B; Department of Physiology, University of Gour Banga, Malda 732103, India. Electronic address: bgiri.emscrl@gmail.com., Haldar S; Department of Biochemistry, Bose Institute, Kolkata 700091, India. Electronic address: subhash.haldar@jcbose.ac.in.
Jazyk: angličtina
Zdroj: Mitochondrion [Mitochondrion] 2023 Jul; Vol. 71, pp. 40-49. Date of Electronic Publication: 2023 May 19.
DOI: 10.1016/j.mito.2023.05.005
Abstrakt: Circulating DNAs are considered as degraded DNA fragments of approximately 50-200 bp, found in blood plasma, consisting of cell-free mitochondrial and nuclear DNA. Such cell-free DNAs in the blood are found to be altered in different pathological conditions including lupus, heart disease, and malignancies. While nuclear DNAs are being used and being developed as a powerful clinical biomarker in liquid biopsies, mitochondrial DNAs (mtDNAs) are associated with inflammatory conditions including cancer progression. Patients with cancer including prostate cancer are found to have measurable concentrations of mitochondrial DNA in circulation in comparison with healthy controls. The plasma content of mitochondrial DNA is dramatically elevated in both prostate cancer patients and mouse models treated with the chemotherapeutic drug. Cell-free mtDNA, in its oxidized form, induced a pro-inflammatory condition and activates NLRP3-mediated inflammasome formation which causes IL-1β-mediated activation of growth factors. On the other hand, interacting with TLR9, mtDNAs trigger NF-κB-mediated complement C3a positive feedback paracrine loop and activate pro-proliferating signaling through upregulating AKT, ERK, and Bcl2 in the prostate tumor microenvironment. In this review, we discuss the growing evidence supporting cell-free mitochondrial DNA copy number, size, and mutations in mtDNA genes as potential prognostic biomarkers in different cancers and targetable prostate cancer therapeutic candidates impacting stromal-epithelial interactions essential for chemotherapy response.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)
Databáze: MEDLINE
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