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Human umbilical cord mesenchymal stem cell-derived exosomes carrying hsa-miRNA-128-3p suppress pancreatic ductal cell carcinoma by inhibiting Galectin-3

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Abstract

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignant tumors of the digestive system. Many patients are diagnosed at an advanced stage and lose eligibility for surgery. Moreover, there are few effective methods for treating pancreatic ductal cell carcinoma. Increasing attention has been given to microRNAs (miRNAs) and their regulatory roles in tumor progression. In this study, we investigated the effects of exosomes extracted from human umbilical cord mesenchymal stem cells (HUCMSCs) carrying hsa-miRNA-128-3p on pancreatic cancer cells.

Methods

Based on existing experimental and database information, we selected Galectin-3, which is associated with pancreatic cancer, and the corresponding upstream hsa-miRNA-128-3p. We extracted HUCMSCs from a fresh umbilical cord, hsa-miRNA-128-3p was transfected into HUCMSCs, and exosomes containing hsa-miRNA-128-3p were extracted and collected. The effect of exosomes rich in hsa-miRNA-128-3p on pancreatic cancer cells was analyzed.

Results

The expression of Galectin-3 in normal pancreatic duct epithelial cells was significantly lower than that in PDAC cell lines. We successfully extracted HUCMSCs from the umbilical cord and transfected hsa-miRNA-128-3p into HUCMSCs. Then we demonstrated that HUCMSC-derived exosomes with hsa-miRNA-128-3p could suppress the proliferation, invasion, and migration of PANC-1 cells in vitro by targeting Galectin-3.

Conclusion

Hsa-miRNA-128-3p could be considered as a potential therapy for pancreatic cancer. We provided a new idea for targeted therapy of PDAC.

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Acknowledgements

This study was supported by grants from Natural Science Foundation of Jiangsu Province (no.BK20211105), the Key Research and Development Plan of Jiangsu Province (no.BE2019692), Postdoctoral Science Foundation of China (Grant No. 2019M661909), The Health Project of Jiangsu Province (Grant No. H2019072), the Social Development Foundation of Nantong City (Grant Nos. MS12020018, MSZ20076, JCZ20065 and MSZ19177).

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Author notes

  1. X. Xie, J. Ji, and X. Chen have contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Affiliated Hospital and Medical School of Nantong University, Nantong, 226001, Jiangsu, China

    X. Xie, J. Ji, J. Wu, Y. Wu, Z. Liu, M. Xiao & B. Bao

  2. Office of Infection Management, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

    X. Chen & H. Chen

  3. Department of Gastroenterology, Second People’s Hospital of Nantong, Nantong, 226001, China

    W. Xu

  4. Medical School of Nantong University Oral Medicine, Nantong, 226001, Jiangsu, China

    S. Zhu

  5. Blood Center of Jiangsu Province, Nanjing, 210000, Jiangsu, China

    Y. Sun

  6. Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

    W. Sai & M. Xiao

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  1. X. Xie
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Correspondence to M. Xiao or B. Bao.

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Xie, X., Ji, J., Chen, X. et al. Human umbilical cord mesenchymal stem cell-derived exosomes carrying hsa-miRNA-128-3p suppress pancreatic ductal cell carcinoma by inhibiting Galectin-3. Clin Transl Oncol 24, 517–531 (2022). https://doi.org/10.1007/s12094-021-02705-7

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