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ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer

Deregulation of noncoding RNAs, including microRNAs (miRs), is implicated in the pathogenesis of many human cancers, including breast cancer. Through extensive analysis of The Cancer Genome Atlas, we found that expression of miR-22-3p is markedly lower in triple-negative breast cancer (TNBC) than in...

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Autores principales: Gorur, Aysegul, Bayraktar, Recep, Ivan, Cristina, Mokhlis, Hamada Ahmed, Bayraktar, Emine, Kahraman, Nermin, Karakas, Didem, Karamil, Selda, Kabil, Nashwa N., Kanlikilicer, Pinar, Aslan, Burcu, Tamer, Lulufer, Wang, Zhihui, Cristini, Vittorio, Lopez-Berestein, Gabriel, Calin, George, Ozpolat, Bulent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868999/
https://www.ncbi.nlm.nih.gov/pubmed/33614241
http://dx.doi.org/10.1016/j.omtn.2021.01.016
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author Gorur, Aysegul
Bayraktar, Recep
Ivan, Cristina
Mokhlis, Hamada Ahmed
Bayraktar, Emine
Kahraman, Nermin
Karakas, Didem
Karamil, Selda
Kabil, Nashwa N.
Kanlikilicer, Pinar
Aslan, Burcu
Tamer, Lulufer
Wang, Zhihui
Cristini, Vittorio
Lopez-Berestein, Gabriel
Calin, George
Ozpolat, Bulent
author_facet Gorur, Aysegul
Bayraktar, Recep
Ivan, Cristina
Mokhlis, Hamada Ahmed
Bayraktar, Emine
Kahraman, Nermin
Karakas, Didem
Karamil, Selda
Kabil, Nashwa N.
Kanlikilicer, Pinar
Aslan, Burcu
Tamer, Lulufer
Wang, Zhihui
Cristini, Vittorio
Lopez-Berestein, Gabriel
Calin, George
Ozpolat, Bulent
author_sort Gorur, Aysegul
collection PubMed
description Deregulation of noncoding RNAs, including microRNAs (miRs), is implicated in the pathogenesis of many human cancers, including breast cancer. Through extensive analysis of The Cancer Genome Atlas, we found that expression of miR-22-3p is markedly lower in triple-negative breast cancer (TNBC) than in normal breast tissue. The restoration of miR-22-3p expression led to significant inhibition of TNBC cell proliferation, colony formation, migration, and invasion. We demonstrated that miR-22-3p reduces eukaryotic elongation factor 2 kinase (eEF2K) expression by directly binding to the 3′ untranslated region of eEF2K mRNA. Inhibition of EF2K expression recapitulated the effects of miR-22-3p on TNBC cell proliferation, motility, invasion, and suppression of phosphatidylinositol 3-kinase/Akt and Src signaling. Systemic administration of miR-22-3p in single-lipid nanoparticles significantly suppressed tumor growth in orthotopic MDA-MB-231 and MDA-MB-436 TNBC models. Evaluation of the tumor response, following miR-22-3p therapy in these models using a novel mathematical model factoring in various in vivo parameters, demonstrated that the therapy is highly effective against TNBC. These findings suggest that miR-22-3p functions as a tumor suppressor by targeting clinically significant oncogenic pathways and that miR-22-3p loss contributes to TNBC growth and progression. The restoration of miR-22-3p expression is a potential novel noncoding RNA-based therapy for TNBC.
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spelling pubmed-78689992021-02-19 ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer Gorur, Aysegul Bayraktar, Recep Ivan, Cristina Mokhlis, Hamada Ahmed Bayraktar, Emine Kahraman, Nermin Karakas, Didem Karamil, Selda Kabil, Nashwa N. Kanlikilicer, Pinar Aslan, Burcu Tamer, Lulufer Wang, Zhihui Cristini, Vittorio Lopez-Berestein, Gabriel Calin, George Ozpolat, Bulent Mol Ther Nucleic Acids Original Article Deregulation of noncoding RNAs, including microRNAs (miRs), is implicated in the pathogenesis of many human cancers, including breast cancer. Through extensive analysis of The Cancer Genome Atlas, we found that expression of miR-22-3p is markedly lower in triple-negative breast cancer (TNBC) than in normal breast tissue. The restoration of miR-22-3p expression led to significant inhibition of TNBC cell proliferation, colony formation, migration, and invasion. We demonstrated that miR-22-3p reduces eukaryotic elongation factor 2 kinase (eEF2K) expression by directly binding to the 3′ untranslated region of eEF2K mRNA. Inhibition of EF2K expression recapitulated the effects of miR-22-3p on TNBC cell proliferation, motility, invasion, and suppression of phosphatidylinositol 3-kinase/Akt and Src signaling. Systemic administration of miR-22-3p in single-lipid nanoparticles significantly suppressed tumor growth in orthotopic MDA-MB-231 and MDA-MB-436 TNBC models. Evaluation of the tumor response, following miR-22-3p therapy in these models using a novel mathematical model factoring in various in vivo parameters, demonstrated that the therapy is highly effective against TNBC. These findings suggest that miR-22-3p functions as a tumor suppressor by targeting clinically significant oncogenic pathways and that miR-22-3p loss contributes to TNBC growth and progression. The restoration of miR-22-3p expression is a potential novel noncoding RNA-based therapy for TNBC. American Society of Gene & Cell Therapy 2021-01-20 /pmc/articles/PMC7868999/ /pubmed/33614241 http://dx.doi.org/10.1016/j.omtn.2021.01.016 Text en © 2021. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Gorur, Aysegul
Bayraktar, Recep
Ivan, Cristina
Mokhlis, Hamada Ahmed
Bayraktar, Emine
Kahraman, Nermin
Karakas, Didem
Karamil, Selda
Kabil, Nashwa N.
Kanlikilicer, Pinar
Aslan, Burcu
Tamer, Lulufer
Wang, Zhihui
Cristini, Vittorio
Lopez-Berestein, Gabriel
Calin, George
Ozpolat, Bulent
ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer
title ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer
title_full ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer
title_fullStr ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer
title_full_unstemmed ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer
title_short ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer
title_sort ncrna therapy with mirna-22-3p suppresses the growth of triple-negative breast cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868999/
https://www.ncbi.nlm.nih.gov/pubmed/33614241
http://dx.doi.org/10.1016/j.omtn.2021.01.016
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