Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo

Zahra Naseri,1 Reza Kazemi Oskuee,2 Mahmoud Reza Jaafari,3,4 Mehdi Forouzandeh Moghadam5 1Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 2Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;...

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Autores principales:	Naseri Z, Oskuee RK, Jaafari MR, Forouzandeh Moghadam M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Exosomes mesenchymal stem cells miR-142-3p APC P2X7R Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/be19fa9b24914defa3c83433f44189ec
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spelling	oai:doaj.org-article:be19fa9b24914defa3c83433f44189ec2021-12-02T03:30:25ZExosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo1178-2013https://doaj.org/article/be19fa9b24914defa3c83433f44189ec2018-11-01T00:00:00Zhttps://www.dovepress.com/exosome-mediated-delivery-of-functionally-active-mirna-142-3p-inhibito-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zahra Naseri,1 Reza Kazemi Oskuee,2 Mahmoud Reza Jaafari,3,4 Mehdi Forouzandeh Moghadam5 1Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 2Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 3Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; 4Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; 5Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Background: Exosomes, widely recognized natural nanovesicles, represent one of the recently discovered modes of intercellular communication due to their ability to transmit crucial cellular information that can be engineered to have robust delivery and targeting capacity. MiR-142-3p, one of the upregulated microRNAs (miRNAs) in many types of breast cancer, activates the canonical Wnt signaling pathway and transactivates the miR-150 expression, and results in the hyperproliferation of cancer cells in vitro and mammary glands in vivo.Materials and methods: In this study, we exploited the exosomes isolated from bone marrow-derived mesenchymal stem cells (MSCs-Exo) to deliver LNA (locked nucleic acid)-modified anti-miR-142-3p oligonucleotides to suppress the expression level of miR-142-3p and miR-150 in 4T1 and TUBO breast cancer cell lines.Results: The in vitro results showed that the MSCs-Exo can efficiently deliver anti-miR-142-3p to reduce the miR-142-3p and miR-150 levels and increase the transcription of the regulatory target genes, APC and P2X7R. We also evaluated in vivo distribution of the MSCs-Exo in tumor-bearing mice. The in vivo result indicated that MSCs-Exo can penetrate the tumor site and are suitable nanovehicles to deliver the inhibitory oligonucleotides into the tumor tissues to downregulate the expression levels of miR-142-3p and miR-150.Conclusion: We showed that MSCs-derived exosomes could be used as a feasible nanovehicle to deliver drug molecules like LNA-anti-miR-142-3p in both in vitro and in vivo studies. Keywords: MSCs-derived exosomes, tumor tropism, Wnt/β-catenin signaling pathway, breast cancer, LNA-antimiR-142-3p Naseri ZOskuee RKJaafari MRForouzandeh Moghadam MDove Medical PressarticleExosomesmesenchymal stem cellsmiR-142-3pAPCP2X7RMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 7727-7747 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Exosomes mesenchymal stem cells miR-142-3p APC P2X7R Medicine (General) R5-920
spellingShingle	Exosomes mesenchymal stem cells miR-142-3p APC P2X7R Medicine (General) R5-920 Naseri Z Oskuee RK Jaafari MR Forouzandeh Moghadam M Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo
description	Zahra Naseri,1 Reza Kazemi Oskuee,2 Mahmoud Reza Jaafari,3,4 Mehdi Forouzandeh Moghadam5 1Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 2Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 3Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; 4Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; 5Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Background: Exosomes, widely recognized natural nanovesicles, represent one of the recently discovered modes of intercellular communication due to their ability to transmit crucial cellular information that can be engineered to have robust delivery and targeting capacity. MiR-142-3p, one of the upregulated microRNAs (miRNAs) in many types of breast cancer, activates the canonical Wnt signaling pathway and transactivates the miR-150 expression, and results in the hyperproliferation of cancer cells in vitro and mammary glands in vivo.Materials and methods: In this study, we exploited the exosomes isolated from bone marrow-derived mesenchymal stem cells (MSCs-Exo) to deliver LNA (locked nucleic acid)-modified anti-miR-142-3p oligonucleotides to suppress the expression level of miR-142-3p and miR-150 in 4T1 and TUBO breast cancer cell lines.Results: The in vitro results showed that the MSCs-Exo can efficiently deliver anti-miR-142-3p to reduce the miR-142-3p and miR-150 levels and increase the transcription of the regulatory target genes, APC and P2X7R. We also evaluated in vivo distribution of the MSCs-Exo in tumor-bearing mice. The in vivo result indicated that MSCs-Exo can penetrate the tumor site and are suitable nanovehicles to deliver the inhibitory oligonucleotides into the tumor tissues to downregulate the expression levels of miR-142-3p and miR-150.Conclusion: We showed that MSCs-derived exosomes could be used as a feasible nanovehicle to deliver drug molecules like LNA-anti-miR-142-3p in both in vitro and in vivo studies. Keywords: MSCs-derived exosomes, tumor tropism, Wnt/β-catenin signaling pathway, breast cancer, LNA-antimiR-142-3p
format	article
author	Naseri Z Oskuee RK Jaafari MR Forouzandeh Moghadam M
author_facet	Naseri Z Oskuee RK Jaafari MR Forouzandeh Moghadam M
author_sort	Naseri Z
title	Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo
title_short	Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo
title_full	Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo
title_fullStr	Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo
title_full_unstemmed	Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo
title_sort	exosome-mediated delivery of functionally active mirna-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/be19fa9b24914defa3c83433f44189ec
work_keys_str_mv	AT naseriz exosomemediateddeliveryoffunctionallyactivemirna1423pinhibitorreducestumorigenicityofbreastcancerinvitroandinvivo AT oskueerk exosomemediateddeliveryoffunctionallyactivemirna1423pinhibitorreducestumorigenicityofbreastcancerinvitroandinvivo AT jaafarimr exosomemediateddeliveryoffunctionallyactivemirna1423pinhibitorreducestumorigenicityofbreastcancerinvitroandinvivo AT forouzandehmoghadamm exosomemediateddeliveryoffunctionallyactivemirna1423pinhibitorreducestumorigenicityofbreastcancerinvitroandinvivo
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Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo

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