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Delivery of miR-155 to retinal pigment epithelial cells mediated by Burkitt’s lymphoma exosomes

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Tumor Biology

Abstract

Exosomes are extracellularly secreted vesicles ranging from 40 to 100 nm in diameter that are thought to play important roles in intercellular communication. Exosomes contain numerous proteins, RNA, and lipids that can affect the status of recipient cells under various pathological conditions. MicroRNAs (miRNAs) are small non-coding RNAs that play a major role in post-transcriptional gene silencing by interacting with the 3′-untranslated regions of target genes. Epstein-Barr virus (EBV) has been reported to induce sustained elevation of cellular miRNAs such as miR-155. We hypothesized that miRNAs delivered by exosomes might affect the angiogenesis of retinal pigment epithelial (RPE) cells. Here, we demonstrated that co-culture of EBV-positive Burkitt’s lymphoma (BL) cells (Raji) with retinal pigment epithelial (ARPE-19) cells increased the level of miR-155 in recipient cells whereas no major difference was detected for co-culture with EBV-negative BL cells (Ramos). Isolated Raji exosomes increased transcriptional and translational levels of VEGF-A in ARPE-19 cells, which was reversely correlated with von Hippel-Lindau expression. A human umbilical vein endothelial cell tube formation assay showed that delivery of ectopic miR-155 rendered ARPE-19 cells proangiogenic. Our results demonstrate that sustained accumulation of miR-155 mediated by exosomes might affect remote recipient cells such as retinal pigment epithelial cells.

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Abbreviations

miR:

MicroRNA

EBV:

Epstein-Barr virus

miR-155:

miRNA-155

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Acknowledgments

This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (R13-2007-023-00000-0) and Basic Science Research Program through NRF funded by the Ministry of Education (NRF-2012R1A1A2006909).

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Authors and Affiliations

  1. Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Bokji-ro 75, Busanjin-gu, Busan, 614-735, Republic of Korea

    Changshin Yoon, Jayoung Kim, Gabin Park, Seonghan Kim, Daejin Kim, Dae Young Hur & Yeong Seok Kim

  2. Department of Pathology, Inje University College of Medicine, Busan, Republic of Korea

    Bomi Kim

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  1. Changshin Yoon
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Correspondence to Yeong Seok Kim.

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Yoon, C., Kim, J., Park, G. et al. Delivery of miR-155 to retinal pigment epithelial cells mediated by Burkitt’s lymphoma exosomes. Tumor Biol. 37, 313–321 (2016). https://doi.org/10.1007/s13277-015-3769-4

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  • DOI: https://doi.org/10.1007/s13277-015-3769-4

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