title: Transfer of functional microRNAs between glioblastoma and microvascular endothelial cells through gap junctions.
abstract: 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.
authors.affiliation: INSERM, U866, Faculty of Medecine, 21000 Dijon, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Thuringer
authors.affiliation: CNRS ERL 7368, STIM laboratory, 86022 Poitiers, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Boucher
authors.affiliation: INSERM, U866, Faculty of Medecine, 21000 Dijon, France.|University of Bourgogne-Franche-Comté, 21000 Dijon, France.
authors.forename: Gaetan
authors.initials: G
authors.lastname: Jego
authors.affiliation: INSERM, U866, Faculty of Medecine, 21000 Dijon, France.|University of Bourgogne-Franche-Comté, 21000 Dijon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pernet
authors.affiliation: CNRS ERL 7368, STIM laboratory, 86022 Poitiers, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Cronier
authors.affiliation: INSERM, U866, Faculty of Medecine, 21000 Dijon, France.
authors.forename: Arlette
authors.initials: A
authors.lastname: Hammann
authors.affiliation: INSERM, U1170, Institut Gustave Roussy, 94508 Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.affiliation: INSERM, U866, Faculty of Medecine, 21000 Dijon, France.|University of Bourgogne-Franche-Comté, 21000 Dijon, France.|CGFL, 21000 Dijon, France.
authors.forename: Carmen
authors.initials: C
authors.lastname: Garrido
mesh_terms: D002450:Cell Communication / Q000235:genetics; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D015870:Gene Expression; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D034443:RNA Transport
chemical_list: C000597931:MIRN-5096 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs
keywords: connexin; gap junction; glioblastoma; microRNA; tubulogenesis