Transfer of functional microRNAs between glioblastoma and microvascular endothelial cells through gap junctions
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Dominique Thuringer1, Jonathan Boucher2, Gaetan Jego1,3, Nicolas Pernet1,3, Laurent Cronier2, Arlette Hammann1, Eric Solary4, Carmen Garrido1,3,5
1INSERM, U866, Faculty of Medecine, 21000 Dijon, France
2CNRS ERL 7368, STIM laboratory, 86022 Poitiers, France
3University of Bourgogne-Franche-Comté, 21000 Dijon, France
4INSERM, U1170, Institut Gustave Roussy, 94508 Villejuif, France
5CGFL, 21000 Dijon, France
Dominique Thuringer, email: [email protected]
Keywords: gap junction, connexin, microRNA, tubulogenesis, glioblastoma
Received: June 30, 2016 Accepted: September 04, 2016 Published: September 20, 2016
Extensive invasion and angiogenesis are hallmark features of malignant glioblastomas. Here, we co-cultured U87 human glioblastoma cells and human microvascular endothelial cells (HMEC) to demonstrate the exchange of microRNAs that initially involve the formation of gap junction communications between the two cell types. The functional inhibition of gap junctions by carbenoxolone blocks the transfer of the anti-tumor miR-145-5p from HMEC to U87, and the transfer of the pro-invasive miR-5096 from U87 to HMEC. These two microRNAs exert opposite effects on angiogenesis in vitro. MiR-5096 was observed to promote HMEC tubulogenesis, initially by increasing Cx43 expression and the formation of heterocellular gap junctions, and secondarily through a gap-junction independent pathway. Our results highlight the importance of microRNA exchanges between tumor and endothelial cells that in part involves the formation of functional gap junctions between the two cell types.
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