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RETRACTED ARTICLE: Human bone marrow-derived mesenchymal stem cell-secreted exosomes overexpressing microRNA-34a ameliorate glioblastoma development via down-regulating MYCN

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This article was retracted on 19 August 2021

A Publisher Correction to this article was published on 03 December 2023

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Abstract

Purpose

Exosomes play important roles in intercellular communication through signaling pathways affecting tumor microenvironment modulation and tumor proliferation, including those in glioblastoma (GBM). As yet, however, limited studies have been conducted on the inhibitory effect of human bone marrow-derived mesenchymal stem cell (hBMSC)-derived exosomes on GBM development. Therefore, we set out to assess the role of hBMSC secreted exosomes, in particular those carrying microRNA-34a (miR-34a), in the development of GBM.

Methods

Microarray-based expression analysis was employed to identify differentially expressed genes and to predict miRNAs regulating MYCN expression. Next, hBMSCs were transfected with a miR-34a mimic or inhibitor after which exosomes were isolated. Proliferation, apoptosis, migration, invasion and temozolomide (TMZ) chemosensitivity of exosome-exposed GBM cells (T-98G, LN229 and A-172) were measured in vitro. The mechanism underlying MYCN regulation was investigated using lentiviral transfections. The in vivo inhibitory effect of exosomal miR-34a was measured in nude mice xenografted with GBM cells through subcutaneous injection of hBMSCs with an upregulated miR34a content.

Results

We found that poorly-expressed miR-34a specifically targeted and negatively regulated the expression of MYCN in GBM cells. In addition we found that miR-34a was delivered to T-98G, LN229 and A-172 GBM cells via hBMSC-derived exosomes. Exogenous overexpression of miR-34a in hBMSC-derived exosomes resulted in inhibition of GBM cell proliferation, invasion, migration and tumorigenesis in vitro and in vivo, while promoting the chemosensitivity of GBM cells to TMZ by silencing MYCN.

Conclusions

From our data we conclude that hBMSC-derived exosomes overexpressing miR-34a may be instrumental for the therapeutic targeting and clinical management of GBM.

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Acknowledgments

We would like to thank our researchers for their hard work and the reviewers for their valuable advice.

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Authors and Affiliations

  1. Department of Neurosurgery, Henan Province People’s Hospital, Zhengzhou University, No. 7, Weiwu Road, Zhengzhou, 450003, Henan Province, People’s Republic of China

    Bin Wang, Zhong-Hua Wu, Ping-Yang Lou & Ming Li

  2. Department of Neurosurgery, People’s Hospital Affiliated with Zhengzhou University, No. 7, Weiwu Road, Zhengzhou, 450003, Henan Province, People’s Republic of China

    Bin Wang, Zhong-Hua Wu, Ping-Yang Lou & Ming Li

  3. Department of Neurosurgery, People’s Hospital Affiliated with Medical college of Henan University, No. 7, Weiwu Road, Zhengzhou, 450003, Henan Province, People’s Republic of China

    Bin Wang, Zhong-Hua Wu, Ping-Yang Lou & Ming Li

  4. Department of Ophthalmology, Henan Province People’s Hospital, Zhengzhou University, Zhengzhou, 450003, People’s Republic of China

    Chang Chai

  5. Center for Translational Medicine, Henan Province People’s Hospital, Zhengzhou University, Zhengzhou, 450003, People’s Republic of China

    Shuang-Yin Han

  6. Department of Neurosurgery, University of Minnesota, Minneapolis, 55455, USA

    Jian-Fang Ning

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  1. Bin Wang
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Contributions

Bin Wang, Zhong-Hua Wu and Ping-Yang Lou designed the study. Chang Chai and Shuang-Yin Han collated the data, designed and developed the database, carried out data analyses and produced the initial draft of the manuscript. Jian-Fang Ning and Ming Li contributed to drafting the manuscript. All authors have contributed to the revision and approved the final submitted manuscript.

Corresponding author

Correspondence to Ming Li.

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None declared.

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This study was carried out and approved by the Institutional Review Board and the Institutional Animal Care and Use Committee of Henan Province People’s Hospital, Zhengzhou University. All patients signed informed consent.

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Wang, B., Wu, ZH., Lou, PY. et al. RETRACTED ARTICLE: Human bone marrow-derived mesenchymal stem cell-secreted exosomes overexpressing microRNA-34a ameliorate glioblastoma development via down-regulating MYCN. Cell Oncol. 42, 783–799 (2019). https://doi.org/10.1007/s13402-019-00461-z

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