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miR526b and miR655 Induce Oxidative Stress in Breast Cancer

In eukaryotes, overproduction of reactive oxygen species (ROS) causes oxidative stress, which contributes to chronic inflammation and cancer. MicroRNAs (miRNAs) are small, endogenously produced RNAs that play a major role in cancer progression. We established that overexpression of miR526b/miR655 pr...

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Autores principales: Shin, Bonita, Feser, Riley, Nault, Braydon, Hunter, Stephanie, Maiti, Sujit, Ugwuagbo, Kingsley Chukwunonso, Majumder, Mousumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720387/
https://www.ncbi.nlm.nih.gov/pubmed/31430859
http://dx.doi.org/10.3390/ijms20164039
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author Shin, Bonita
Feser, Riley
Nault, Braydon
Hunter, Stephanie
Maiti, Sujit
Ugwuagbo, Kingsley Chukwunonso
Majumder, Mousumi
author_facet Shin, Bonita
Feser, Riley
Nault, Braydon
Hunter, Stephanie
Maiti, Sujit
Ugwuagbo, Kingsley Chukwunonso
Majumder, Mousumi
author_sort Shin, Bonita
collection PubMed
description In eukaryotes, overproduction of reactive oxygen species (ROS) causes oxidative stress, which contributes to chronic inflammation and cancer. MicroRNAs (miRNAs) are small, endogenously produced RNAs that play a major role in cancer progression. We established that overexpression of miR526b/miR655 promotes aggressive breast cancer phenotypes. Here, we investigated the roles of miR526b/miR655 in oxidative stress in breast cancer using in vitro and in silico assays. miRNA-overexpression in MCF7 cells directly enhances ROS and superoxide (SO) production, detected with fluorescence assays. We found that cell-free conditioned media contain extracellular miR526b/miR655 and treatment with these miRNA-conditioned media causes overproduction of ROS/SO in MCF7 and primary cells (HUVECs). Thioredoxin Reductase 1 (TXNRD1) is an oxidoreductase that maintains ROS/SO concentration. Overexpression of TXNRD1 is associated with breast cancer progression. We observed that miR526b/miR655 overexpression upregulates TXNRD1 expression in MCF7 cells, and treatment with miRNA-conditioned media upregulates TXNRD1 in both MCF7 and HUVECs. Bioinformatic analysis identifies two negative regulators of TXNRD1, TCF21 and PBRM1, as direct targets of miR526b/miR655. We validated that TCF21 and PBRM1 were significantly downregulated with miRNA upregulation, establishing a link between miR526b/miR655 and TXNRD1. Finally, treatments with oxidative stress inducers such as H(2)O(2) or miRNA-conditioned media showed an upregulation of miR526b/miR655 expression in MCF7 cells, indicating that oxidative stress also induces miRNA overexpression. This study establishes the dynamic functions of miR526b/miR655 in oxidative stress induction in breast cancer.
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spelling pubmed-67203872019-09-10 miR526b and miR655 Induce Oxidative Stress in Breast Cancer Shin, Bonita Feser, Riley Nault, Braydon Hunter, Stephanie Maiti, Sujit Ugwuagbo, Kingsley Chukwunonso Majumder, Mousumi Int J Mol Sci Article In eukaryotes, overproduction of reactive oxygen species (ROS) causes oxidative stress, which contributes to chronic inflammation and cancer. MicroRNAs (miRNAs) are small, endogenously produced RNAs that play a major role in cancer progression. We established that overexpression of miR526b/miR655 promotes aggressive breast cancer phenotypes. Here, we investigated the roles of miR526b/miR655 in oxidative stress in breast cancer using in vitro and in silico assays. miRNA-overexpression in MCF7 cells directly enhances ROS and superoxide (SO) production, detected with fluorescence assays. We found that cell-free conditioned media contain extracellular miR526b/miR655 and treatment with these miRNA-conditioned media causes overproduction of ROS/SO in MCF7 and primary cells (HUVECs). Thioredoxin Reductase 1 (TXNRD1) is an oxidoreductase that maintains ROS/SO concentration. Overexpression of TXNRD1 is associated with breast cancer progression. We observed that miR526b/miR655 overexpression upregulates TXNRD1 expression in MCF7 cells, and treatment with miRNA-conditioned media upregulates TXNRD1 in both MCF7 and HUVECs. Bioinformatic analysis identifies two negative regulators of TXNRD1, TCF21 and PBRM1, as direct targets of miR526b/miR655. We validated that TCF21 and PBRM1 were significantly downregulated with miRNA upregulation, establishing a link between miR526b/miR655 and TXNRD1. Finally, treatments with oxidative stress inducers such as H(2)O(2) or miRNA-conditioned media showed an upregulation of miR526b/miR655 expression in MCF7 cells, indicating that oxidative stress also induces miRNA overexpression. This study establishes the dynamic functions of miR526b/miR655 in oxidative stress induction in breast cancer. MDPI 2019-08-19 /pmc/articles/PMC6720387/ /pubmed/31430859 http://dx.doi.org/10.3390/ijms20164039 Text en © 2019 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
Shin, Bonita
Feser, Riley
Nault, Braydon
Hunter, Stephanie
Maiti, Sujit
Ugwuagbo, Kingsley Chukwunonso
Majumder, Mousumi
miR526b and miR655 Induce Oxidative Stress in Breast Cancer
title miR526b and miR655 Induce Oxidative Stress in Breast Cancer
title_full miR526b and miR655 Induce Oxidative Stress in Breast Cancer
title_fullStr miR526b and miR655 Induce Oxidative Stress in Breast Cancer
title_full_unstemmed miR526b and miR655 Induce Oxidative Stress in Breast Cancer
title_short miR526b and miR655 Induce Oxidative Stress in Breast Cancer
title_sort mir526b and mir655 induce oxidative stress in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720387/
https://www.ncbi.nlm.nih.gov/pubmed/31430859
http://dx.doi.org/10.3390/ijms20164039
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