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

Naseri, Z. and Oskuee, R. K. and Jaafari, M. R. and Moghadam, M. F. (2018) Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo. International Journal of Nanomedicine, 13. pp. 7727-7747.

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

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Abstract

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. © 2018 Naseri et al.

Item Type: Article
Additional Information: Cited By :16 Export Date: 16 February 2020 Correspondence Address: Moghadam, M.F.; Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Jalal ale Ahmad Highway, PO Box 14115-331, Iran; email: foroz@modares.ac.ir
Uncontrolled Keywords: Breast cancer LNA-antimiR-142-3p MSCs-derived exosomes Tumor tropism Wnt/β-catenin signaling pathway locked nucleic acid modified anti miRNA 142 3p oligonucleotide microRNA microRNA 142 3p microRNA 150 oligonucleotide unclassified drug fluorescent dye locked nucleic acid Mirn142 microRNA, mouse Mirn150 microRNA, mouse animal cell animal experiment animal model APC gene Article bone marrow derived mesenchymal stem cell carcinogenicity controlled study drug delivery system exosome female gene gene expression genetic transcription in vitro study in vivo study mouse nonhuman P2X7R gene animal antagonists and inhibitors antibody specificity apoptosis Bagg albino mouse breast tumor carcinogenesis cell proliferation chemistry gene transfer genetics human mesenchymal stem cell metabolism pathology tumor cell line ultrastructure Animals Breast Neoplasms Cell Line, Tumor Exosomes Fluorescent Dyes Gene Transfer Techniques Humans Mesenchymal Stem Cells Mice, Inbred BALB C MicroRNAs Oligonucleotides Organ Specificity
Subjects: WP Gynecology
WQ Obstetrics
QU Biochemistry
QV pharmacology
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 08 May 2020 14:28
Last Modified: 08 May 2020 14:28
URI: http://eprints.mums.ac.ir/id/eprint/17448

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