Open AccessPattern of cell‐to‐cell transfer of micro RNA by gap junction and its effect on the proliferation of glioma cells
Author(s) -
Peng Yuexia,
Wang Xiyan,
Guo Yunquan,
Peng Fuhua,
Zheng Ningze,
He Bo,
Ge Hui,
Tao Liang,
Wang Qin
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14029
Subject(s) - connexin , gap junction , microrna , microbiology and biotechnology , small interfering rna , gene silencing , biology , cell , downregulation and upregulation , chemistry , cell culture , cancer research , transfection , gene , biochemistry , genetics , intracellular
Micro RNA is expected to be a novel therapeutic tool for tumors. Gap junctions facilitate the transfer of micro RNA , which exerts biological effects on tumor cells. However, the length of micro RNA that can pass through certain gap junctions composed of specific connexin remains unknown. To address this question, the present study investigated the permeability of gap junctions composed of various connexins, including connexin 43, connexin 32 or connexin 37, to micro RNA s consisting of 18‐27 nucleotides in glioma cells and cervical cancer cells. Results indicated that all of the micro RNA s were able to be transferred from donor glioma cells to neighboring cells through the connexin 43 composed gap junction, but not the gap junctions composed of connexin 32 or connexin 37, in cervical cancer cells. Downregulation of the function of gap junctions comprising connexin 43 by pharmacological inhibition and sh RNA significantly decreased the transfer of these micro RNA s. In contrast, gap junction enhancers and overexpression of connexin 43 effectively increased these transfers. In glioma cells, cell proliferation was inhibited by micro RNA ‐34a. Additionally, these effects of micro RNA ‐34a were significantly enhanced by overexpression of connexin 43 in U251 cells, indicating that gap junctions play an important role in the antitumor effect of micro RNA by transfer of micro RNA to neighboring cells. Our data are the first to clarify the pattern of micro RNA transmission through gap junctions and provide novel insights to show that antitumor micro RNA s should be combined with connexin 43 or a connexin 43 enhancer, not connexin 32 or connexin 37, in order to improve the therapeutic effect.