Modulation of the inwardly rectifying potassium channel Kir4.1 by the pro-invasive miR-5096 in glioblastoma cells
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Dominique Thuringer1, Gaetan Chanteloup1, Jonathan Boucher2, Nicolas Pernet1,3, Christophe Boudesco1, Gaetan Jego1,3, Aurelien Chatelier2, Patrick Bois2, Jessica Gobbo1,4, Laurent Cronier2, Eric Solary5 and Carmen Garrido1,3
1INSERM, U1231, Faculty of Medicine, 21000 Dijon, France
2CNRS ERL 7368, STIM Laboratory, 86022 Poitiers, France
3University of Bourgogne-Franche-Comté, 21000 Dijon, France
4CGFL, Department of Medical Oncology, 21000 Dijon, France
5INSERM, U1170, Institut Gustave Roussy, 94508 Villejuif, France
Dominique Thuringer, email: email@example.com
Keywords: K+ current, exosome, migration, microRNA, filopodia
Received: January 06, 2017 Accepted: March 22, 2017 Published: April 07, 2017
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.
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