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miR-1 inhibits the proliferation of breast cancer stem cells by targeting EVI-1

PURPOSE: Breast cancer stem cells (BCSCs) have been regarded as the key factor for treatment failure in breast cancer. The abnormal expression of miRNAs plays a significant role in different tumor types. However, the role of miR-1 in breast cancer remains poorly understood. The purpose of this study...

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Autores principales: Wu, Lei, Wang, Tianyi, He, Dongning, Li, Xiaoxi, Jiang, Youhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287527/
https://www.ncbi.nlm.nih.gov/pubmed/30584335
http://dx.doi.org/10.2147/OTT.S188836
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author Wu, Lei
Wang, Tianyi
He, Dongning
Li, Xiaoxi
Jiang, Youhong
author_facet Wu, Lei
Wang, Tianyi
He, Dongning
Li, Xiaoxi
Jiang, Youhong
author_sort Wu, Lei
collection PubMed
description PURPOSE: Breast cancer stem cells (BCSCs) have been regarded as the key factor for treatment failure in breast cancer. The abnormal expression of miRNAs plays a significant role in different tumor types. However, the role of miR-1 in breast cancer remains poorly understood. The purpose of this study was to evaluate the effects of miR-1 on the proliferation and apoptosis of BCSCs. MATERIALS AND METHODS: CD44(+)/CD24(−/low)/epithelial-specific antigen(+) BCSCs were isolated by flow cytometry. Real-time PCR and Western blotting were used to determine the expression of miRNAs, mRNAs, and epithelial–mesenchymal transition (EMT)-related genes. Cell proliferation and apoptosis were measured using the Cell Counting Kit-8 assay and Annexin V-fluorescein isothiocyanate flow cytometry, respectively. Luciferase reporter assay was used to verify whether miR-1 targeted ecotropic virus integration-1 (EVI-1). The role of miR-1 in breast cancer in vivo was evaluated using BCSCs xenograft mouse models. RESULTS: In this study, we demonstrated that miR-1 was significantly downregulated in breast cancer tissues compared to the adjacent non-tumor tissues. The luciferase reporter assay verified that EVI-1 was a direct target of miR-1, and upregulation of miR-1 negatively correlated with the expression of EVI-1 in BCSCs at both the transcriptional and posttranslational levels. Furthermore, overexpression of miR-1 inhibited BCSCs proliferation and promoted apoptosis, which was reversed by the overexpression of EVI-1. In addition, we demonstrated that aberrant expression of miR-1 could regulate EMT-related genes in BCSCs. Finally, immunohistochemical staining demonstrated that EVI-1 expression was decreased in BCSCs tumors following intra-tumoral miR-1 agomir treatment compared to the control group. CONCLUSION: miR-1 can negatively regulate the expression of EVI-1 and, thus, affect BCSCs proliferation, apoptosis, and EMT-related markers. Taken together, these findings demonstrate that miR-1 could be employed as a therapeutic strategy in the treatment of breast cancer.
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spelling pubmed-62875272018-12-24 miR-1 inhibits the proliferation of breast cancer stem cells by targeting EVI-1 Wu, Lei Wang, Tianyi He, Dongning Li, Xiaoxi Jiang, Youhong Onco Targets Ther Original Research PURPOSE: Breast cancer stem cells (BCSCs) have been regarded as the key factor for treatment failure in breast cancer. The abnormal expression of miRNAs plays a significant role in different tumor types. However, the role of miR-1 in breast cancer remains poorly understood. The purpose of this study was to evaluate the effects of miR-1 on the proliferation and apoptosis of BCSCs. MATERIALS AND METHODS: CD44(+)/CD24(−/low)/epithelial-specific antigen(+) BCSCs were isolated by flow cytometry. Real-time PCR and Western blotting were used to determine the expression of miRNAs, mRNAs, and epithelial–mesenchymal transition (EMT)-related genes. Cell proliferation and apoptosis were measured using the Cell Counting Kit-8 assay and Annexin V-fluorescein isothiocyanate flow cytometry, respectively. Luciferase reporter assay was used to verify whether miR-1 targeted ecotropic virus integration-1 (EVI-1). The role of miR-1 in breast cancer in vivo was evaluated using BCSCs xenograft mouse models. RESULTS: In this study, we demonstrated that miR-1 was significantly downregulated in breast cancer tissues compared to the adjacent non-tumor tissues. The luciferase reporter assay verified that EVI-1 was a direct target of miR-1, and upregulation of miR-1 negatively correlated with the expression of EVI-1 in BCSCs at both the transcriptional and posttranslational levels. Furthermore, overexpression of miR-1 inhibited BCSCs proliferation and promoted apoptosis, which was reversed by the overexpression of EVI-1. In addition, we demonstrated that aberrant expression of miR-1 could regulate EMT-related genes in BCSCs. Finally, immunohistochemical staining demonstrated that EVI-1 expression was decreased in BCSCs tumors following intra-tumoral miR-1 agomir treatment compared to the control group. CONCLUSION: miR-1 can negatively regulate the expression of EVI-1 and, thus, affect BCSCs proliferation, apoptosis, and EMT-related markers. Taken together, these findings demonstrate that miR-1 could be employed as a therapeutic strategy in the treatment of breast cancer. Dove Medical Press 2018-12-06 /pmc/articles/PMC6287527/ /pubmed/30584335 http://dx.doi.org/10.2147/OTT.S188836 Text en © 2018 Wu et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Wu, Lei
Wang, Tianyi
He, Dongning
Li, Xiaoxi
Jiang, Youhong
miR-1 inhibits the proliferation of breast cancer stem cells by targeting EVI-1
title miR-1 inhibits the proliferation of breast cancer stem cells by targeting EVI-1
title_full miR-1 inhibits the proliferation of breast cancer stem cells by targeting EVI-1
title_fullStr miR-1 inhibits the proliferation of breast cancer stem cells by targeting EVI-1
title_full_unstemmed miR-1 inhibits the proliferation of breast cancer stem cells by targeting EVI-1
title_short miR-1 inhibits the proliferation of breast cancer stem cells by targeting EVI-1
title_sort mir-1 inhibits the proliferation of breast cancer stem cells by targeting evi-1
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287527/
https://www.ncbi.nlm.nih.gov/pubmed/30584335
http://dx.doi.org/10.2147/OTT.S188836
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