Modulation of the inwardly rectifying potassium channel Kir4.1 by the pro-invasive miR-5096 in glioblastoma cells.

Abstract : 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.
Liste complète des métadonnées

https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01559384
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : lundi 10 juillet 2017 - 16:21:42
Dernière modification le : vendredi 23 février 2018 - 12:18:07

Lien texte intégral

Identifiants

Citation

Dominique Thuringer, Gaetan Chanteloup, Jonathan Boucher, Nicolas Pernet, Christophe Boudesco, et al.. Modulation of the inwardly rectifying potassium channel Kir4.1 by the pro-invasive miR-5096 in glioblastoma cells.. Oncotarget, Impact journals, 2017, pp.37681-37693. 〈www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path=16949&pubmed-linkout=1〉. 〈10.18632/oncotarget.16949〉. 〈hal-01559384〉

Partager

Métriques

Consultations de la notice

91