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Modulation of Ferroptosis by microRNAs in Human Cancer

Ferroptosis is a cell death pathway triggered by an imbalance between the production of oxidants and antioxidants, which plays an emerging role in tumorigenesis. It is mainly regulated at three different levels including iron metabolism, the antioxidant response, and lipid metabolism. Epigenetic dys...

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Autores principales: Velkova, Irena, Pasino, Martina, Khalid, Zumama, Menichini, Paola, Martorana, Emanuele, Izzotti, Alberto, Pulliero, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221902/
https://www.ncbi.nlm.nih.gov/pubmed/37240889
http://dx.doi.org/10.3390/jpm13050719
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author Velkova, Irena
Pasino, Martina
Khalid, Zumama
Menichini, Paola
Martorana, Emanuele
Izzotti, Alberto
Pulliero, Alessandra
author_facet Velkova, Irena
Pasino, Martina
Khalid, Zumama
Menichini, Paola
Martorana, Emanuele
Izzotti, Alberto
Pulliero, Alessandra
author_sort Velkova, Irena
collection PubMed
description Ferroptosis is a cell death pathway triggered by an imbalance between the production of oxidants and antioxidants, which plays an emerging role in tumorigenesis. It is mainly regulated at three different levels including iron metabolism, the antioxidant response, and lipid metabolism. Epigenetic dysregulation is a “hallmark” of human cancer, with nearly half of all human cancers harboring mutations in epigenetic regulators such as microRNA. While being the crucial player in controlling gene expression at the mRNA level, microRNAs have recently been shown to modulate cancer growth and development via the ferroptosis pathway. In this scenario, some miRNAs have a function in upregulating, while others play a role in inhibiting ferroptosis activity. The investigation of validated targets using the miRBase, miRTarBase, and miRecords platforms identified 13 genes that appeared enriched for iron metabolism, lipid peroxidation, and antioxidant defense; all are recognized contributors of tumoral suppression or progression phenotypes. This review summarizes and discuss the mechanism by which ferroptosis is initiated through an imbalance in the three pathways, the potential function of microRNAs in the control of this process, and a description of the treatments that have been shown to have an impact on the ferroptosis in cancer along with potential novel effects.
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spelling pubmed-102219022023-05-28 Modulation of Ferroptosis by microRNAs in Human Cancer Velkova, Irena Pasino, Martina Khalid, Zumama Menichini, Paola Martorana, Emanuele Izzotti, Alberto Pulliero, Alessandra J Pers Med Review Ferroptosis is a cell death pathway triggered by an imbalance between the production of oxidants and antioxidants, which plays an emerging role in tumorigenesis. It is mainly regulated at three different levels including iron metabolism, the antioxidant response, and lipid metabolism. Epigenetic dysregulation is a “hallmark” of human cancer, with nearly half of all human cancers harboring mutations in epigenetic regulators such as microRNA. While being the crucial player in controlling gene expression at the mRNA level, microRNAs have recently been shown to modulate cancer growth and development via the ferroptosis pathway. In this scenario, some miRNAs have a function in upregulating, while others play a role in inhibiting ferroptosis activity. The investigation of validated targets using the miRBase, miRTarBase, and miRecords platforms identified 13 genes that appeared enriched for iron metabolism, lipid peroxidation, and antioxidant defense; all are recognized contributors of tumoral suppression or progression phenotypes. This review summarizes and discuss the mechanism by which ferroptosis is initiated through an imbalance in the three pathways, the potential function of microRNAs in the control of this process, and a description of the treatments that have been shown to have an impact on the ferroptosis in cancer along with potential novel effects. MDPI 2023-04-24 /pmc/articles/PMC10221902/ /pubmed/37240889 http://dx.doi.org/10.3390/jpm13050719 Text en © 2023 by the authors. 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
Velkova, Irena
Pasino, Martina
Khalid, Zumama
Menichini, Paola
Martorana, Emanuele
Izzotti, Alberto
Pulliero, Alessandra
Modulation of Ferroptosis by microRNAs in Human Cancer
title Modulation of Ferroptosis by microRNAs in Human Cancer
title_full Modulation of Ferroptosis by microRNAs in Human Cancer
title_fullStr Modulation of Ferroptosis by microRNAs in Human Cancer
title_full_unstemmed Modulation of Ferroptosis by microRNAs in Human Cancer
title_short Modulation of Ferroptosis by microRNAs in Human Cancer
title_sort modulation of ferroptosis by micrornas in human cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221902/
https://www.ncbi.nlm.nih.gov/pubmed/37240889
http://dx.doi.org/10.3390/jpm13050719
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