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The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer

Metformin, a drug approved for diabetes type II treatment, has been associated with a reduction in the incidence of breast cancer and metastasis and increased survival in diabetic breast cancer patients. High levels of miR-26a expression have been proposed as one of the possible mechanisms for this...

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Autores principales: Cabello, Paula, Pineda, Begoña, Tormo, Eduardo, Lluch, Ana, Eroles, Pilar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000695/
https://www.ncbi.nlm.nih.gov/pubmed/27517917
http://dx.doi.org/10.3390/ijms17081298
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author Cabello, Paula
Pineda, Begoña
Tormo, Eduardo
Lluch, Ana
Eroles, Pilar
author_facet Cabello, Paula
Pineda, Begoña
Tormo, Eduardo
Lluch, Ana
Eroles, Pilar
author_sort Cabello, Paula
collection PubMed
description Metformin, a drug approved for diabetes type II treatment, has been associated with a reduction in the incidence of breast cancer and metastasis and increased survival in diabetic breast cancer patients. High levels of miR-26a expression have been proposed as one of the possible mechanisms for this effect; likewise, this miRNA has also been associated with survival/apoptosis processes in breast cancer. Our aim was to evaluate if miR-26a and some of its targets could mediate the effect of metformin in breast cancer. The viability of MDA-MB-231, MDA-MB-468, and MCF-7 breast cancer cell lines was evaluated with an MTT assay after ectopic overexpression and/or downregulation of miR-26a. Similarly, the expression levels of the miR-26a targets CASP3, CCNE2, ABL2, APAF1, XIAP, BCL-2, PTEN, p53, E2F3, CDC25A, BCL2L1, MCL-1, EZH2, and MTDH were assessed by quantitative polymerase chain reaction (PCR). The effect of metformin treatment on breast cancer cell viability and miR-26a, BCL-2, PTEN, MCL-1, EZH2, and MTDH modulation were evaluated. Wound healing experiments were performed to analyze the effect of miR-26a and metformin treatment on cell migration. MiR-26a overexpression resulted in a reduction in cell viability that was partially recovered by inhibiting it. E2F3, MCL-1, EZH2, MTDH, and PTEN were downregulated by miR-26a and the PTEN (phosphatase and tensin homolog) protein was also reduced after miR-26a overexpression. Metformin treatment reduced breast cancer cell viability, increased miR-26a expression, and led to a reduction in BCL-2, EZH2, and PTEN expression. miR-26a inhibition partly prevents the metformin viability effect and the PTEN and EZH2 expression reduction. Our results indicate that metformin effectively reduces breast cancer cell viability and suggests that the effects of the drug are mediated by an increase in miR-26a expression and a reduction of its targets, PTEN and EHZ2 Thus, the use of metformin in breast cancer treatment constitutes a promising potential breast cancer therapy.
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spelling pubmed-50006952016-09-01 The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer Cabello, Paula Pineda, Begoña Tormo, Eduardo Lluch, Ana Eroles, Pilar Int J Mol Sci Article Metformin, a drug approved for diabetes type II treatment, has been associated with a reduction in the incidence of breast cancer and metastasis and increased survival in diabetic breast cancer patients. High levels of miR-26a expression have been proposed as one of the possible mechanisms for this effect; likewise, this miRNA has also been associated with survival/apoptosis processes in breast cancer. Our aim was to evaluate if miR-26a and some of its targets could mediate the effect of metformin in breast cancer. The viability of MDA-MB-231, MDA-MB-468, and MCF-7 breast cancer cell lines was evaluated with an MTT assay after ectopic overexpression and/or downregulation of miR-26a. Similarly, the expression levels of the miR-26a targets CASP3, CCNE2, ABL2, APAF1, XIAP, BCL-2, PTEN, p53, E2F3, CDC25A, BCL2L1, MCL-1, EZH2, and MTDH were assessed by quantitative polymerase chain reaction (PCR). The effect of metformin treatment on breast cancer cell viability and miR-26a, BCL-2, PTEN, MCL-1, EZH2, and MTDH modulation were evaluated. Wound healing experiments were performed to analyze the effect of miR-26a and metformin treatment on cell migration. MiR-26a overexpression resulted in a reduction in cell viability that was partially recovered by inhibiting it. E2F3, MCL-1, EZH2, MTDH, and PTEN were downregulated by miR-26a and the PTEN (phosphatase and tensin homolog) protein was also reduced after miR-26a overexpression. Metformin treatment reduced breast cancer cell viability, increased miR-26a expression, and led to a reduction in BCL-2, EZH2, and PTEN expression. miR-26a inhibition partly prevents the metformin viability effect and the PTEN and EZH2 expression reduction. Our results indicate that metformin effectively reduces breast cancer cell viability and suggests that the effects of the drug are mediated by an increase in miR-26a expression and a reduction of its targets, PTEN and EHZ2 Thus, the use of metformin in breast cancer treatment constitutes a promising potential breast cancer therapy. MDPI 2016-08-10 /pmc/articles/PMC5000695/ /pubmed/27517917 http://dx.doi.org/10.3390/ijms17081298 Text en © 2016 by the authors; 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cabello, Paula
Pineda, Begoña
Tormo, Eduardo
Lluch, Ana
Eroles, Pilar
The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer
title The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer
title_full The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer
title_fullStr The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer
title_full_unstemmed The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer
title_short The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer
title_sort antitumor effect of metformin is mediated by mir-26a in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000695/
https://www.ncbi.nlm.nih.gov/pubmed/27517917
http://dx.doi.org/10.3390/ijms17081298
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