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Noncoding RNAs Controlling Oxidative Stress in Cancer

SIMPLE SUMMARY: Mitochondria in cancer cells produce reactive oxygen species, inducing a vicious cycle between oxidative stress, genomic instability, and cancer development. However, too high oxidative stress kills tumor cells. Cancer cells protect themselves directly by increasing antioxidant expre...

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Autor principal: Holvoet, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954372/
https://www.ncbi.nlm.nih.gov/pubmed/36831498
http://dx.doi.org/10.3390/cancers15041155
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author Holvoet, Paul
author_facet Holvoet, Paul
author_sort Holvoet, Paul
collection PubMed
description SIMPLE SUMMARY: Mitochondria in cancer cells produce reactive oxygen species, inducing a vicious cycle between oxidative stress, genomic instability, and cancer development. However, too high oxidative stress kills tumor cells. Cancer cells protect themselves directly by increasing antioxidant expression. In addition, shifting the phenotype of immune cells from ant-oncogenic to pro-oncogenic reduces reactive oxygen levels within the tumor microenvironment to maintain tumor growth. This review shows how noncoding RNAs may regulate mitochondrial function, antioxidant expression, and immune cell reprogramming. Interestingly, noncoding RNAs in microvesicles secreted by mesenchymal stem cells, cancer-associated fibroblasts, and cancer cells contribute to this immune cell reprogramming. Further research on the role of noncoding RNAs in the communication between cell types in the tumor microenvironment is warranted. ABSTRACT: Mitochondria in cancer cells tend to overproduce reactive oxygen species (ROS), inducing a vicious cycle between mitochondria, ROS, genomic instability, and cancer development. The first part of this review deals with the role of noncoding RNAs in regulating mitochondrial ROS production and the expression of antioxidants in cancer cells, preventing the increase of ROS in the tumor microenvironment. In addition, cytotoxic T and natural killer cells release high levels of ROS, inducing cell death, while anti-immune regulatory T cells, tumor-associated M2 macrophages, and myeloid-derived suppressor cells, at least at the initial stage of tumor growth, release low levels of ROS supporting tumor growth. Therefore, this review’s second part deals with noncoding RNAs’ role in regulating the metabolic reprogramming of immune cells about ROS release. Furthermore, the enrichment of noncoding RNAs in microvesicles allows communication between cell types in a tumor and between a tumor and tumor-adjacent tissues. Therefore, the third part illustrates how noncoding RNA-containing microvesicles secreted by mesenchymal stem cells and primary tumor cells may primarily aid the shift of immune cells to a pro-oncogenic phenotype. Conversely, microvesicles released by tumor-adjacent tissues may have the opposite effect. Our review reveals that a specific noncoding RNA may affect oxidative stress by several mechanisms, which may have opposite effects on tumor growth. Furthermore, they may be involved in mechanisms other than regulating oxidative stress, which may level out their effects on oxidative stress and tumor growth. In addition, several noncoding RNAs might share a specific function, making it very unlikely that intervening with only one of these noncoding RNAs will block this particular mechanism. Overall, further validation of the interaction between noncoding RNAs about cancer types and stages of tumor development is warranted.
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spelling pubmed-99543722023-02-25 Noncoding RNAs Controlling Oxidative Stress in Cancer Holvoet, Paul Cancers (Basel) Review SIMPLE SUMMARY: Mitochondria in cancer cells produce reactive oxygen species, inducing a vicious cycle between oxidative stress, genomic instability, and cancer development. However, too high oxidative stress kills tumor cells. Cancer cells protect themselves directly by increasing antioxidant expression. In addition, shifting the phenotype of immune cells from ant-oncogenic to pro-oncogenic reduces reactive oxygen levels within the tumor microenvironment to maintain tumor growth. This review shows how noncoding RNAs may regulate mitochondrial function, antioxidant expression, and immune cell reprogramming. Interestingly, noncoding RNAs in microvesicles secreted by mesenchymal stem cells, cancer-associated fibroblasts, and cancer cells contribute to this immune cell reprogramming. Further research on the role of noncoding RNAs in the communication between cell types in the tumor microenvironment is warranted. ABSTRACT: Mitochondria in cancer cells tend to overproduce reactive oxygen species (ROS), inducing a vicious cycle between mitochondria, ROS, genomic instability, and cancer development. The first part of this review deals with the role of noncoding RNAs in regulating mitochondrial ROS production and the expression of antioxidants in cancer cells, preventing the increase of ROS in the tumor microenvironment. In addition, cytotoxic T and natural killer cells release high levels of ROS, inducing cell death, while anti-immune regulatory T cells, tumor-associated M2 macrophages, and myeloid-derived suppressor cells, at least at the initial stage of tumor growth, release low levels of ROS supporting tumor growth. Therefore, this review’s second part deals with noncoding RNAs’ role in regulating the metabolic reprogramming of immune cells about ROS release. Furthermore, the enrichment of noncoding RNAs in microvesicles allows communication between cell types in a tumor and between a tumor and tumor-adjacent tissues. Therefore, the third part illustrates how noncoding RNA-containing microvesicles secreted by mesenchymal stem cells and primary tumor cells may primarily aid the shift of immune cells to a pro-oncogenic phenotype. Conversely, microvesicles released by tumor-adjacent tissues may have the opposite effect. Our review reveals that a specific noncoding RNA may affect oxidative stress by several mechanisms, which may have opposite effects on tumor growth. Furthermore, they may be involved in mechanisms other than regulating oxidative stress, which may level out their effects on oxidative stress and tumor growth. In addition, several noncoding RNAs might share a specific function, making it very unlikely that intervening with only one of these noncoding RNAs will block this particular mechanism. Overall, further validation of the interaction between noncoding RNAs about cancer types and stages of tumor development is warranted. MDPI 2023-02-10 /pmc/articles/PMC9954372/ /pubmed/36831498 http://dx.doi.org/10.3390/cancers15041155 Text en © 2023 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Holvoet, Paul
Noncoding RNAs Controlling Oxidative Stress in Cancer
title Noncoding RNAs Controlling Oxidative Stress in Cancer
title_full Noncoding RNAs Controlling Oxidative Stress in Cancer
title_fullStr Noncoding RNAs Controlling Oxidative Stress in Cancer
title_full_unstemmed Noncoding RNAs Controlling Oxidative Stress in Cancer
title_short Noncoding RNAs Controlling Oxidative Stress in Cancer
title_sort noncoding rnas controlling oxidative stress in cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954372/
https://www.ncbi.nlm.nih.gov/pubmed/36831498
http://dx.doi.org/10.3390/cancers15041155
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