Delivery of miR-155 to retinal pigment epithelial cells mediated by Burkitt’s lymphoma exosomes
- 697 Downloads
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.
KeywordsExosome miR-155 EBV Burkitt’s lymphoma Retinal pigment epithelial cell
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).
- 4.Xie Y, Bai O, Zhang H, Yuan J, Zong S, Chibbar R, et al. Membrane-bound hsp70-engineered myeloma cell-derived exosomes stimulate more efficient cd8(+) ctl- and nk-mediated antitumour immunity than exosomes released from heat-shocked tumour cells expressing cytoplasmic hsp70. J Cell Mol Med. 2010;14:2655–66.CrossRefPubMedGoogle Scholar
- 7.Mulcahy LA, Pink RC, Carter DR. Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles. 2014;3.Google Scholar
- 31.Hong GK, Kumar P, Wang PL, Damania B, Gulley ML, Delecluse HJ, et al. Epstein-Barr virus lytic infection is required for efficient production of the angiogenesis factor vascular endothelial growth factor in lymphoblastoid cell lines. J Virol. 2005;79:13984–92.CrossRefPubMedPubMedCentralGoogle Scholar