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Human umbilical cord mesenchymal stem cell-derived exosomes inhibit migration and invasion of breast cancer cells via miR-21-5p/ZNF367 pathway

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Abstract

Background

Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-exos) exhibit various roles in breast cancer development. The molecular mechanisms underlying hucMSC-exos in breast cancer cells are not fully clear. In the current study, we set out to investigate the downstream signaling pathways of hucMSC-exos in MCF-7 cells, a commonly used cell line to study breast cancer.

Methods

hucMSC-exos’ effects on MCF-7 cells were examined using immunocytochemistry. An inhibitor and a mimic of miR-21-5p were administered. The mRNA and protein levels of ZNF367 were analyzed using real-time quantitative reverse transcription PCR (qRT-PCR)and western blotting. Transwell assays were used to measure invasion and migration. Dual-luciferase assays were performed to investigate the binding sites between miR-21-5p and ZNF367. To manipulate expression, an overexpressing of ZNF367 approach was utilized.

Results

We confirmed that hucMSC-exos can be internalized by MCF-7 cells. hucMSC-exos dramatically inhibited migration and invasion behaviors through downregulation of ZNF367 and upregulation of miR-21-5p. miR-21-5p directly binds on 3′UTR of ZNF367. miR-21-5p mimic partially abolished overexpressed ZNF367-induced migration and invasion. In breast cancer tissues, there was a negative correlation between miR-21-5p and ZNF367 levels. The similar results were also obtained in human breast cancer MDA-MB-231 cells.

Conclusion

husMSC-exos are anti-oncogenic in MCS-7 cells. husMSC-exos suppress ZNF367 expression and promote miR-21-5p expression. miR-21-5p opposes ZNF367’s actions during breast cancer development. miR-21-5p direct binds ZNF367 3′UTR to inhibit ZNF367 expression. The interaction between miR-21-5p and ZNF367 may serve as a future therapeutic approach to improve breast cancer prognosis.

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Acknowledgements

We sincerely acknowledged the assistance given by the QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China for the present research.

Funding

None.

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Author notes

  1. Lei Du and Xingguang Tao: co-first author.

Authors and Affiliations

  1. General Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China

    Lei Du

  2. Department of Orthopedics, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, QingPu District Central Hospital Shanghai, Shanghai, 201700, China

    Xingguang Tao

  3. Department of General Surgery, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, QingPu District Central Hospital Shanghai, No.1158, Gong Yuan Dong Road , Shanghai, 201700, China

    Xiaowei Shen

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  1. Lei Du
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  2. Xingguang Tao
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  3. Xiaowei Shen
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by XS, LD and XT. The first draft of the manuscript was written by XS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Xiaowei Shen.

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12282_2021_1218_MOESM1_ESM.jpg

Supplementary Figure S1: Lentiviral vector mediates ZNF367 overexpression in MCF-7 cells. A and B. The relative mRNA and protein contents of ZNF367 were significantly overexpressed in MCF-7 cells that were transfected with oeZNF367. *** p < 0.001 vs oeNC (JPG 921 KB).

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Du, L., Tao, X. & Shen, X. Human umbilical cord mesenchymal stem cell-derived exosomes inhibit migration and invasion of breast cancer cells via miR-21-5p/ZNF367 pathway. Breast Cancer 28, 829–837 (2021). https://doi.org/10.1007/s12282-021-01218-z

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  • DOI: https://doi.org/10.1007/s12282-021-01218-z

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