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Metabolic reprogramming of metastatic breast cancer and melanoma by let-7a microRNA
Let-7 microRNAs (miRNAs) are highly conserved well-established promoters of terminal differentiation that are expressed in healthy adult tissues and frequently repressed in cancer cells. The tumor suppressive role of let-7 in a variety of cancers in vitro and in vivo has been widely documented and p...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385863/ https://www.ncbi.nlm.nih.gov/pubmed/25669981 |
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author | Serguienko, Anastassia Grad, Iwona Wennerstrøm, Anna B. Meza-Zepeda, Leonardo A. Thiede, Bernd Stratford, Eva W. Myklebost, Ola Munthe, Else |
author_facet | Serguienko, Anastassia Grad, Iwona Wennerstrøm, Anna B. Meza-Zepeda, Leonardo A. Thiede, Bernd Stratford, Eva W. Myklebost, Ola Munthe, Else |
author_sort | Serguienko, Anastassia |
collection | PubMed |
description | Let-7 microRNAs (miRNAs) are highly conserved well-established promoters of terminal differentiation that are expressed in healthy adult tissues and frequently repressed in cancer cells. The tumor suppressive role of let-7 in a variety of cancers in vitro and in vivo has been widely documented and prompted these miRNAs to be candidate genes for miRNA replacement therapy. In this study we described a new role of let-7a in reprogramming cancer metabolism, recently identified as a new hallmark of cancer. We show that let-7a down-regulates key anabolic enzymes and increases both oxidative phosphorylation and glycolysis in triple-negative breast cancer and metastatic melanoma cell lines. Strikingly, the accelerated glycolysis coexists with drastically reduced cancer features. Moreover, let-7a causes mitochondrial ROS production concomitant with the up-regulation of oxidative stress responsive genes. To exploit these increased ROS levels for therapeutic purposes, we combined let-7a transfection with the chemotherapeutic drug doxorubicin. In both cancer types let-7a increased cell sensitivity to doxorubicin. Pre-treatment with N-acetyl cysteine (NAC) totally abolished this effect, indicating that the increased doxorubicin sensitivity of let-7a cells depends on the redox pathway. We thus have demonstrated that let-7a plays a prominent role in regulating energy metabolism in cancer cells, further expanding its therapeutic potential. |
format | Online Article Text |
id | pubmed-4385863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-43858632015-04-14 Metabolic reprogramming of metastatic breast cancer and melanoma by let-7a microRNA Serguienko, Anastassia Grad, Iwona Wennerstrøm, Anna B. Meza-Zepeda, Leonardo A. Thiede, Bernd Stratford, Eva W. Myklebost, Ola Munthe, Else Oncotarget Research Paper Let-7 microRNAs (miRNAs) are highly conserved well-established promoters of terminal differentiation that are expressed in healthy adult tissues and frequently repressed in cancer cells. The tumor suppressive role of let-7 in a variety of cancers in vitro and in vivo has been widely documented and prompted these miRNAs to be candidate genes for miRNA replacement therapy. In this study we described a new role of let-7a in reprogramming cancer metabolism, recently identified as a new hallmark of cancer. We show that let-7a down-regulates key anabolic enzymes and increases both oxidative phosphorylation and glycolysis in triple-negative breast cancer and metastatic melanoma cell lines. Strikingly, the accelerated glycolysis coexists with drastically reduced cancer features. Moreover, let-7a causes mitochondrial ROS production concomitant with the up-regulation of oxidative stress responsive genes. To exploit these increased ROS levels for therapeutic purposes, we combined let-7a transfection with the chemotherapeutic drug doxorubicin. In both cancer types let-7a increased cell sensitivity to doxorubicin. Pre-treatment with N-acetyl cysteine (NAC) totally abolished this effect, indicating that the increased doxorubicin sensitivity of let-7a cells depends on the redox pathway. We thus have demonstrated that let-7a plays a prominent role in regulating energy metabolism in cancer cells, further expanding its therapeutic potential. Impact Journals LLC 2014-12-29 /pmc/articles/PMC4385863/ /pubmed/25669981 Text en Copyright: © 2015 Serguienko et al. http://creativecommons.org/licenses/by/2.5/ 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 credited. |
spellingShingle | Research Paper Serguienko, Anastassia Grad, Iwona Wennerstrøm, Anna B. Meza-Zepeda, Leonardo A. Thiede, Bernd Stratford, Eva W. Myklebost, Ola Munthe, Else Metabolic reprogramming of metastatic breast cancer and melanoma by let-7a microRNA |
title | Metabolic reprogramming of metastatic breast cancer and melanoma by let-7a microRNA |
title_full | Metabolic reprogramming of metastatic breast cancer and melanoma by let-7a microRNA |
title_fullStr | Metabolic reprogramming of metastatic breast cancer and melanoma by let-7a microRNA |
title_full_unstemmed | Metabolic reprogramming of metastatic breast cancer and melanoma by let-7a microRNA |
title_short | Metabolic reprogramming of metastatic breast cancer and melanoma by let-7a microRNA |
title_sort | metabolic reprogramming of metastatic breast cancer and melanoma by let-7a microrna |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385863/ https://www.ncbi.nlm.nih.gov/pubmed/25669981 |
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