Gap Junctions Enhance the Antiproliferative Effect of MicroRNA-124-3p in Glioblastoma Cells

Journal of Cellular Physiology
Zhang SuzhiWang Qin

Abstract

MicroRNA (miRNA) holds promise as a novel therapeutic tool for cancer treatment. However, the transfection efficiency of current delivery systems represents a bottleneck for clinical applications. Here, we demonstrate that gap junctions mediate an augmentative effect on the antiproliferation mediated by miR-124-3p in U87 and C6 glioblastoma cells. The functional inhibition of gap junctions using either siRNA or pharmacological inhibition eliminated the miR-124-3p-mediated antiproliferation, whereas the enhancement of gap junctions with retinoic acid treatment augmented this miR-124-3p-mediated antiproliferation. A similar effect was observed in glioblastoma xenograft models. More importantly, patch clamp and co-culture assays demonstrated the transmission of miR-124-3p through gap junction channels into adjacent cells. In further exploring the impact of gap junction-mediated transport of miR-124-3p on miR-124-3p target pathways, we found that miR-124-3p inhibited glioblastoma cell growth in part by decreasing the protein expression of cyclin-dependent kinase 6, leading to cell cycle arrest at the G0 /G1 phase; moreover, pharmacological regulation of gap junctions affected this cell cycle arrest. In conclusion, our results indic...Continue Reading

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