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Delivery of LNA-antimiR-142-3p by Mesenchymal Stem Cells-Derived Exosomes to Breast Cancer Stem Cells Reduces Tumorigenicity

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Abstract

Exosomes, nano-sized cell-derived vesicles, have been employed as non-synthetic carriers of various pharmaceutics in numerous studies. As higher expression levels of miR-142-3p and miR-150 in breast cancer stem cells (BCSCs) are associated with their clonogenic and tumorigenic capabilities, the present study aims to exploit the mesenchymal stem cells-derived exosomes (MSCs-Exo) to deliver LNA-antimiR-142-3p into MCF7-derived cancer stem-like cells to suppress expression levels of miR-142-3p and miR-150 in order to reduce clonogenicity and tumorigenicity. Our results indicated that the MSCs-Exo can efficiently deliver the LNA-antimiR-142-3p to breast cancer stem-like cells to reduce the miR-142-3p and miR-150 expression levels. Furthermore, the inhibition of the oncomiRs with the delivery of LNA-antimiR-142-3p resulted in a significant reduction of clone-formation and tumor-initiating abilities of the MCF7-derived cancer stem-like cells. In conclusion, we showed that MSCs-derived exosomes could be used as a feasible nanovehicles to deliver RNA-based therapeutics into BCSCs to improve the cancer treatment.

Highlights

  • Exosomes secreted by bone marrow-derived mesenchymal stem cells efficiently transfer the LNA-antimiR-142-3p to breast cancer stem cells.

  • Exosomes-mediated delivery of LNA-antimiR-142-3p to the breast cancer stem cells leads to downregulation of miR-142-3p and miR-150 and the overexpression of target genes.

  • Delivery of LNA-antimiR-142-3p by the exosomes reduces the colony formation capability of breast cancer stem cells in vitro.

  • Inhibition of miR-142-3p and miR-150 by the LNA-antimiR-142-3p loaded exosomes reduces the tumorigenicity of breast cancer stem cells in vivo.

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Acknowledgments

We are grateful to our colleagues and PhD students, for help and support during this work, in the Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran. We also thank Mrs. Karen Fascioli for editing the manuscript.

Funding

This research was funded by Mashhad University of Medical Sciences and Tarbiat Modares University, Tehran (NO.931289); and a grant from cancer research center of cancer institute of Iran (Shams cancer charity, Grant No: 37604–202–01-97). The funding sources played no decisive role in collection, analysis, the interpretation of the data, as well as decision to submit for publication.

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Authors and Affiliations

  1. Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Zahra naseri

  2. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Reza Kazemi Oskuee

  3. Department of medical biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, P.O.Box:14115-331, Jalal ale Ahmad Highway, Tehran, Iran

    Mehdi forouzandeh-moghadam

  4. Biotechnology Research Center, Pharmaceutical Technology Institude, Mashhad University of Medical Sciences, P.O. Box: 91775-1365, Mashhad, Iran

    Mahmoud Reza Jaafari

  5. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box: 91775-1365, Mashhad, Iran

    Mahmoud Reza Jaafari

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  1. Zahra naseri
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Correspondence to Mehdi forouzandeh-moghadam or Mahmoud Reza Jaafari.

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naseri, Z., Oskuee, R.K., forouzandeh-moghadam, M. et al. Delivery of LNA-antimiR-142-3p by Mesenchymal Stem Cells-Derived Exosomes to Breast Cancer Stem Cells Reduces Tumorigenicity. Stem Cell Rev and Rep 16, 541–556 (2020). https://doi.org/10.1007/s12015-019-09944-w

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