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Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer

microRNA-22 (miR-22) is an oncogenic miRNA whose up-regulation promotes epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis in hormone-responsive breast cancer. Here we show that miR-22 plays a key role in triple negative breast cancer (TNBC) by promoting EMT and aggressiveness i...

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Autores principales: Panella, Riccardo, Cotton, Cody A., Maymi, Valerie A., Best, Sachem, Berry, Kelsey E., Lee, Samuel, Batalini, Felipe, Vlachos, Ioannis S., Clohessy, John G., Kauppinen, Sakari, Paolo Pandolfi, Pier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216774/
https://www.ncbi.nlm.nih.gov/pubmed/37239141
http://dx.doi.org/10.3390/biomedicines11051470
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author Panella, Riccardo
Cotton, Cody A.
Maymi, Valerie A.
Best, Sachem
Berry, Kelsey E.
Lee, Samuel
Batalini, Felipe
Vlachos, Ioannis S.
Clohessy, John G.
Kauppinen, Sakari
Paolo Pandolfi, Pier
author_facet Panella, Riccardo
Cotton, Cody A.
Maymi, Valerie A.
Best, Sachem
Berry, Kelsey E.
Lee, Samuel
Batalini, Felipe
Vlachos, Ioannis S.
Clohessy, John G.
Kauppinen, Sakari
Paolo Pandolfi, Pier
author_sort Panella, Riccardo
collection PubMed
description microRNA-22 (miR-22) is an oncogenic miRNA whose up-regulation promotes epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis in hormone-responsive breast cancer. Here we show that miR-22 plays a key role in triple negative breast cancer (TNBC) by promoting EMT and aggressiveness in 2D and 3D cell models and a mouse xenograft model of human TNBC, respectively. Furthermore, we report that miR-22 inhibition using an LNA-modified antimiR-22 compound is effective in reducing EMT both in vitro and in vivo. Importantly, pharmacologic inhibition of miR-22 suppressed metastatic spread and markedly prolonged survival in mouse xenograft models of metastatic TNBC highlighting the potential of miR-22 silencing as a new therapeutic strategy for the treatment of TNBC.
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spelling pubmed-102167742023-05-27 Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer Panella, Riccardo Cotton, Cody A. Maymi, Valerie A. Best, Sachem Berry, Kelsey E. Lee, Samuel Batalini, Felipe Vlachos, Ioannis S. Clohessy, John G. Kauppinen, Sakari Paolo Pandolfi, Pier Biomedicines Article microRNA-22 (miR-22) is an oncogenic miRNA whose up-regulation promotes epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis in hormone-responsive breast cancer. Here we show that miR-22 plays a key role in triple negative breast cancer (TNBC) by promoting EMT and aggressiveness in 2D and 3D cell models and a mouse xenograft model of human TNBC, respectively. Furthermore, we report that miR-22 inhibition using an LNA-modified antimiR-22 compound is effective in reducing EMT both in vitro and in vivo. Importantly, pharmacologic inhibition of miR-22 suppressed metastatic spread and markedly prolonged survival in mouse xenograft models of metastatic TNBC highlighting the potential of miR-22 silencing as a new therapeutic strategy for the treatment of TNBC. MDPI 2023-05-18 /pmc/articles/PMC10216774/ /pubmed/37239141 http://dx.doi.org/10.3390/biomedicines11051470 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Panella, Riccardo
Cotton, Cody A.
Maymi, Valerie A.
Best, Sachem
Berry, Kelsey E.
Lee, Samuel
Batalini, Felipe
Vlachos, Ioannis S.
Clohessy, John G.
Kauppinen, Sakari
Paolo Pandolfi, Pier
Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer
title Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer
title_full Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer
title_fullStr Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer
title_full_unstemmed Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer
title_short Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer
title_sort targeting of microrna-22 suppresses tumor spread in a mouse model of triple-negative breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216774/
https://www.ncbi.nlm.nih.gov/pubmed/37239141
http://dx.doi.org/10.3390/biomedicines11051470
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