Abstract
Intercellular communications within the cancer microenvironment coordinate the assembly of various cell types. Exosomes are mediators of intercellular communication in immune signaling, tumor promotion, stress responses, and angiogenesis. The present research aimed to determine whether miRNAs secreted from human bronchial epithelial (HBE) cells transformed by 1.0 μM arsenite are transferred into normal HBE cells and are functionally active in the recipient cells. The results show that miR-21 is involved in exosome-mediated intercellular communication between neoplastic and normal HBE cells. Exosomes derived from transformed HBE cells stimulated proliferation of normal HBE cells, whereas exosomes from miR-21 depleted cells failed to stimulate proliferation. In normal HBE cells, the expression of phosphatase and tensin homolog, a target gene for miR-21, was increased by exosomal miR-21, indicating that exogenous miRNAs, via exosomal transport, function-like endogenous miRNAs. Concordantly, specific reduction of miR-21 content in exosome-producing transformed cells abolished the stimulation of proliferation by exosomes. Collectively, the data indicate that transformed HBE cells release exosomes containing miR-21, stimulating proliferation in neighboring normal HBE cells and supporting the concept that exosomal miRNAs are involved in cell–cell communication during carcinogenesis induced by environmental chemicals.
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Acknowledgments
The authors wish to thank Donald L. Hill (University of Alabama at Birmingham, USA) for editing. This work was supported by the Natural Science Foundations of China (30872146, 81072327, and 81273114), the Research Fund for the Doctoral Program of Higher Education of China (20103234110005), the Key Program of Educational Commission of Jiangsu Province of China (11KJA330002), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (2010).
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The authors listed participated in the design, execution, and analysis of these experiments. All have read the manuscript and have agreed to submit it in its current form for consideration for publication in this journal. They declare that there are no conflict of interests.
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Yuan Xu and Fei Luo authors contributed equally.
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Xu, Y., Luo, F., Liu, Y. et al. Exosomal miR-21 derived from arsenite-transformed human bronchial epithelial cells promotes cell proliferation associated with arsenite carcinogenesis. Arch Toxicol 89, 1071–1082 (2015). https://doi.org/10.1007/s00204-014-1291-x
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DOI: https://doi.org/10.1007/s00204-014-1291-x