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Gap Junctions Enhance the Antiproliferative Effect of MicroRNA‐124‐3p in Glioblastoma Cells
Author(s) -
Suzhi Zhang,
Liang Tao,
Yuexia Peng,
Lucy Liu,
Xiaoting Hong,
Yuan Zhang,
Qin Wang
Publication year - 2015
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24982
Subject(s) - gap junction , cell cycle , connexin , microbiology and biotechnology , microrna , cancer research , bystander effect , chemistry , cell cycle checkpoint , transfection , cell growth , cell culture , u87 , glioblastoma , cell , biology , intracellular , immunology , gene , biochemistry , genetics
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 G 0 /G 1 phase; moreover, pharmacological regulation of gap junctions affected this cell cycle arrest. In conclusion, our results indicate that the “bystander” effects of functional gap junctions composed of connexin 43 enhance the antitumor effect of miR‐124‐3p in glioblastoma cells by transferring miR‐124‐3p to adjacent cells, thereby enhancing G 0 /G 1 cell cycle arrest. These observations provide a new guiding strategy for the clinical application of miRNA therapy in tumor treatment. J. Cell. Physiol. 230: 2476–2488, 2015. © 2015 Wiley Periodicals, Inc.