Oncotarget

Research Papers:

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

Dominique Thuringer _, Gaetan Chanteloup, Jonathan Boucher, Nicolas Pernet, Christophe Boudesco, Gaetan Jego, Aurelien Chatelier, Patrick Bois, Jessica Gobbo, Laurent Cronier, Eric Solary and Carmen Garrido

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Oncotarget. 2017; 8:37681-37693. https://doi.org/10.18632/oncotarget.16949

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Abstract

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

Correspondence to:

Dominique Thuringer, email: dominique.thuringer@u-bourgogne.fr

Keywords: K+ current, exosome, migration, microRNA, filopodia

Received: January 06, 2017     Accepted: March 22, 2017     Published: April 07, 2017

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.


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