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Delivery of miR-381-3p Mimic by Mesenchymal Stem Cell-Derived Exosomes Inhibits Triple Negative Breast Cancer Aggressiveness; an In Vitro Study

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Abstract

Recent investigations have emphasized the role of aberrant expression of microRNAs (miRNAs) in progression of almost all types of cancers. Exosomes, membrane-enclosed natural nanovesicles, transport cellular contents, including proteins, mRNAs, and miRNAs, between cells. Unique features of exosomes make them an appropriate carrier for drug delivery. miRNA-381 is one of the downregulated miRNAs in several cancers including triple-negative breast cancer (TNBC) and restoration of its expression in TNBC cells can restrict their migratory ability through targeting several signaling pathways. In current study, we exploited the exosomes isolated from adipose-derived mesenchymal stem cells (ADMSC-exosomes) to deliver miR-381 mimic to MDA-MB-231 cells to elucidate their effects on TNBC cells. The effects of miR-381 loaded ADMSC-exosomes on proliferation, apoptosis, migration, and invasion of MDA-MB-231 cells were analyzed. Our results indicated that ADMSC-exosomes were successfully isolated and internalized by MDA-MB-231 cells. miR-381 mimic was efficiently delivered to MDA-MB-231 cells by ADMSC-exosomes. miR-381 loaded ADMSC-exosomes significantly downregulated the expression of epithelial to mesenchymal transition (EMT) related genes and proteins. Notably, miR-381 loaded ADMSC-exosomes inhibited proliferation, migration, and invasion capacity of MDA-MB-231 and promoted their apoptosis in vitro. Taken together, we showed that ADMSC-exosomes could be used as efficient nanocarriers for RNA-based therapies.

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Acknowledgements

The authors should thank Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran for providing technical support.

Funding

This project funded by School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences,Tehran, Iran (Contact grant No: 11985).

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Authors and Affiliations

  1. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Samaneh Shojaei, Kazem Sharifi, Mohammad Salehi & Samira Mohammadi-Yeganeh

  2. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Seyed Mahmoud Hashemi

  3. Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Seyed Mahmoud Hashemi

  4. Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hossein Ghanbarian & Samira Mohammadi-Yeganeh

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  1. Samaneh Shojaei
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Correspondence to Samira Mohammadi-Yeganeh.

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This study was executed under supervision of ethical committee of shahid Beheshti University of Medical Sciences, Tehran, Iran (ethical code: IR.SBMU.REC.1397.004).

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Shojaei, S., Hashemi, S.M., Ghanbarian, H. et al. Delivery of miR-381-3p Mimic by Mesenchymal Stem Cell-Derived Exosomes Inhibits Triple Negative Breast Cancer Aggressiveness; an In Vitro Study. Stem Cell Rev and Rep 17, 1027–1038 (2021). https://doi.org/10.1007/s12015-020-10089-4

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