MicroRNA-210 Regulates Mitochondrial Free Radical Response to Hypoxia and Krebs Cycle in Cancer Cells by Targeting Iron Sulfur Cluster Protein ISCU

BACKGROUND: Hypoxia in cancers results in the upregulation of hypoxia inducible factor 1 (HIF-1) and a microRNA, hsa-miR-210 (miR-210) which is associated with a poor prognosis. METHODS AND FINDINGS: In human cancer cell lines and tumours, we found that miR-210 targets the mitochondrial iron sulfur...

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Autores principales: Favaro, Elena, Ramachandran, Anassuya, McCormick, Robert, Gee, Harriet, Blancher, Christine, Crosby, Meredith, Devlin, Cecilia, Blick, Christopher, Buffa, Francesca, Li, Ji-Liang, Vojnovic, Borivoj, Pires das Neves, Ricardo, Glazer, Peter, Iborra, Francisco, Ivan, Mircea, Ragoussis, Jiannis, Harris, Adrian L.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859946/
https://www.ncbi.nlm.nih.gov/pubmed/20436681
http://dx.doi.org/10.1371/journal.pone.0010345
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author Favaro, Elena
Ramachandran, Anassuya
McCormick, Robert
Gee, Harriet
Blancher, Christine
Crosby, Meredith
Devlin, Cecilia
Blick, Christopher
Buffa, Francesca
Li, Ji-Liang
Vojnovic, Borivoj
Pires das Neves, Ricardo
Glazer, Peter
Iborra, Francisco
Ivan, Mircea
Ragoussis, Jiannis
Harris, Adrian L.
author_facet Favaro, Elena
Ramachandran, Anassuya
McCormick, Robert
Gee, Harriet
Blancher, Christine
Crosby, Meredith
Devlin, Cecilia
Blick, Christopher
Buffa, Francesca
Li, Ji-Liang
Vojnovic, Borivoj
Pires das Neves, Ricardo
Glazer, Peter
Iborra, Francisco
Ivan, Mircea
Ragoussis, Jiannis
Harris, Adrian L.
author_sort Favaro, Elena
collection PubMed
description BACKGROUND: Hypoxia in cancers results in the upregulation of hypoxia inducible factor 1 (HIF-1) and a microRNA, hsa-miR-210 (miR-210) which is associated with a poor prognosis. METHODS AND FINDINGS: In human cancer cell lines and tumours, we found that miR-210 targets the mitochondrial iron sulfur scaffold protein ISCU, required for assembly of iron-sulfur clusters, cofactors for key enzymes involved in the Krebs cycle, electron transport, and iron metabolism. Down regulation of ISCU was the major cause of induction of reactive oxygen species (ROS) in hypoxia. ISCU suppression reduced mitochondrial complex 1 activity and aconitase activity, caused a shift to glycolysis in normoxia and enhanced cell survival. Cancers with low ISCU had a worse prognosis. CONCLUSIONS: Induction of these major hallmarks of cancer show that a single microRNA, miR-210, mediates a new mechanism of adaptation to hypoxia, by regulating mitochondrial function via iron-sulfur cluster metabolism and free radical generation.
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spelling pubmed-28599462010-04-30 MicroRNA-210 Regulates Mitochondrial Free Radical Response to Hypoxia and Krebs Cycle in Cancer Cells by Targeting Iron Sulfur Cluster Protein ISCU Favaro, Elena Ramachandran, Anassuya McCormick, Robert Gee, Harriet Blancher, Christine Crosby, Meredith Devlin, Cecilia Blick, Christopher Buffa, Francesca Li, Ji-Liang Vojnovic, Borivoj Pires das Neves, Ricardo Glazer, Peter Iborra, Francisco Ivan, Mircea Ragoussis, Jiannis Harris, Adrian L. PLoS One Research Article BACKGROUND: Hypoxia in cancers results in the upregulation of hypoxia inducible factor 1 (HIF-1) and a microRNA, hsa-miR-210 (miR-210) which is associated with a poor prognosis. METHODS AND FINDINGS: In human cancer cell lines and tumours, we found that miR-210 targets the mitochondrial iron sulfur scaffold protein ISCU, required for assembly of iron-sulfur clusters, cofactors for key enzymes involved in the Krebs cycle, electron transport, and iron metabolism. Down regulation of ISCU was the major cause of induction of reactive oxygen species (ROS) in hypoxia. ISCU suppression reduced mitochondrial complex 1 activity and aconitase activity, caused a shift to glycolysis in normoxia and enhanced cell survival. Cancers with low ISCU had a worse prognosis. CONCLUSIONS: Induction of these major hallmarks of cancer show that a single microRNA, miR-210, mediates a new mechanism of adaptation to hypoxia, by regulating mitochondrial function via iron-sulfur cluster metabolism and free radical generation. Public Library of Science 2010-04-26 /pmc/articles/PMC2859946/ /pubmed/20436681 http://dx.doi.org/10.1371/journal.pone.0010345 Text en Favaro et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Favaro, Elena
Ramachandran, Anassuya
McCormick, Robert
Gee, Harriet
Blancher, Christine
Crosby, Meredith
Devlin, Cecilia
Blick, Christopher
Buffa, Francesca
Li, Ji-Liang
Vojnovic, Borivoj
Pires das Neves, Ricardo
Glazer, Peter
Iborra, Francisco
Ivan, Mircea
Ragoussis, Jiannis
Harris, Adrian L.
MicroRNA-210 Regulates Mitochondrial Free Radical Response to Hypoxia and Krebs Cycle in Cancer Cells by Targeting Iron Sulfur Cluster Protein ISCU
title MicroRNA-210 Regulates Mitochondrial Free Radical Response to Hypoxia and Krebs Cycle in Cancer Cells by Targeting Iron Sulfur Cluster Protein ISCU
title_full MicroRNA-210 Regulates Mitochondrial Free Radical Response to Hypoxia and Krebs Cycle in Cancer Cells by Targeting Iron Sulfur Cluster Protein ISCU
title_fullStr MicroRNA-210 Regulates Mitochondrial Free Radical Response to Hypoxia and Krebs Cycle in Cancer Cells by Targeting Iron Sulfur Cluster Protein ISCU
title_full_unstemmed MicroRNA-210 Regulates Mitochondrial Free Radical Response to Hypoxia and Krebs Cycle in Cancer Cells by Targeting Iron Sulfur Cluster Protein ISCU
title_short MicroRNA-210 Regulates Mitochondrial Free Radical Response to Hypoxia and Krebs Cycle in Cancer Cells by Targeting Iron Sulfur Cluster Protein ISCU
title_sort microrna-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein iscu
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859946/
https://www.ncbi.nlm.nih.gov/pubmed/20436681
http://dx.doi.org/10.1371/journal.pone.0010345
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