Modulation of the inwardly rectifying potassium channel Kir4.1 by the pro-invasive miR-5096 in glioblastoma cells.
Fiche publication
Date publication
avril 2017
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GARRIDO Carmen, Dr GOBBO Jessica, Dr JEGO Gaëtan, Dr THURINGER Dominique, Mr PERNET Nicolas
Tous les auteurs :
Thuringer D, Chanteloup G, Boucher J, Pernet N, Boudesco C, Jego G, Chatelier A, Bois P, Gobbo J, Cronier L, Solary E, Garrido C
Lien Pubmed
Résumé
Inwardly rectifying potassium channels (Kir), and especially the barium-sensitive Kir4.1 encoded by KCNJ10, are key regulators of glial functions. A lower expression or mislocation of Kir4.1 is detected in human brain tumors. MicroRNAs participate in the regulation of ionic channels and associated neurologic disorders. Here, we analyze effects of miR-5096 on the Kir4.1 expression and function in two glioblastoma cell lines, U87 and U251. Using whole-cell patch-clamp and western-blot analysis, we show that cell loading with miR-5096 decreases the Kir4.1 protein level and associated K+ current. Cell treatment with barium, a Kir4.1 blocker, or cell loading of miR-5096 both increase the outgrowth of filopodia in glioma cells, as observed by time-lapse microscopy. Knocking-down Kir4.1 expression by siRNA transfection similarly increased both filopodia formation and invasiveness of glioma cells as observed in Boyden chamber assay. MiR-5096 also promotes the release of extracellular vesicles by which it increases its own transfer to surrounding cells, in a Kir4.1-dependent manner in U251 but not in U87. Altogether, our results validate Kir4.1 as a miR-5096 target to promote invasion of glioblastoma cells. Our data highlight the complexity of microRNA effects and the role of K+ channels in cancer.
Mots clés
K+ current, exosome, filopodia, microRNA, migration
Référence
Oncotarget. 2017 Apr;: