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piRNA-823 delivered by multiple myeloma-derived extracellular vesicles promoted tumorigenesis through re-educating endothelial cells in the tumor environment

Oncogene volume 38, pages 5227–5238 (2019)Cite this article

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Abstract

Extracellular vesicles (EVs) can carry a wide array of RNAs in the tumor microenvironment, and are crucial for communication between tumor and surrounding stromal cells, including endothelial cells. Piwi-interacting RNAs (piRNAs) are important regulators implicated in the pathogenesis of multiple myeloma (MM). However, little is understood about the role of piRNA-823 in intercellular communication between MM and endothelial cells. In this study, we found that piRNA-823 mainly accumulated in EVs from peripheral blood of MM patients and EVs derived from MM cells (MM-derived-EVs). Increased piRNA-823 expression was associated with late stages and poor prognosis of MM. The MM-derived-EVs effectively transferred piRNA-823 to EA.hy926 endothelial cells. The piRNA-823 mimic and inhibitor were designed to upregulate or to suppress the endogenous function of piRNA-823. Transfection with piRNA-823 mimic or treatment with MM-derived-EVs significantly promoted the proliferation, tube formation, and invasion of EA.hy926 cells by enhancing the expression of VEGF, IL-6, and ICAM-1 and attenuating apoptosis. EA.hy926 cells transfected with piRNA-823 mimic or pre-treated with MM-derived-EVs promoted the growth of xenograft MM in mice. In contrast, the transfection with piRNA-823 inhibitor or treatment with EVs from piRNA-823 inhibitor-transfected-MM cells had diametrically opposite effects. Our findings demonstrated that piRNA-823 carried by MM-derived-EVs is essential for the re-education of ECs toward a unique environment amenable to the growth of MM cells by altering its biological characteristics. Our findings may pave the way for the development of new piRNA-mediated prognostic stratification and therapeutic strategies for MM.

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Acknowledgements

The authors would like to thank all the participants for their kind cooperation. The research was supported by the National Natural Science Foundation of P.R China (no. 30500686, for Q-LW) and (no. 81770219, for Q-LW).

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  1. These authors contributed equally: Beibei Li, Jiaxin Hong, Mei Hong

Authors and Affiliations

  1. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Beibei Li, Jiaxin Hong, Mei Hong, Yajun Wang, Tingting Yu, Sibin Zang & Qiuling Wu

  2. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Jiaxin Hong

  3. Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China

    Mei Hong

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Li, B., Hong, J., Hong, M. et al. piRNA-823 delivered by multiple myeloma-derived extracellular vesicles promoted tumorigenesis through re-educating endothelial cells in the tumor environment. Oncogene 38, 5227–5238 (2019). https://doi.org/10.1038/s41388-019-0788-4

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