Inhibitory effects of miRNAs in astrocytes on C6 glioma progression via connexin 43

In many types of tumor cells, cell communication via gap junction is decreased or missing. Therefore, cancer cells acquire unique cytosolic environments that differ from those of normal cells. This study assessed the differences in microRNA (miRNA) expression between cancer and normal cells. MicroRNA microarray analysis revealed five miRNAs that were highly expressed in normal astrocytes compared with that in C6 gliomas. To determine whether these miRNAs could pass through gap junctions, connexin 43 was expressed in C6 glioma cells and co-cultured with normal astrocytes. The co-culture experiment showed the possibility that miR-152-3p and miR-143-3p propagate from normal astrocytes to C6 glioma in connexin 43-dependent and -independent manners, respectively. Moreover, we established C6 glioma cells that expressed miR-152-3p or miR-143-3p. Although the proliferation of these miRNA-expressing C6 glioma cells did not differ from that of empty vectors introduced in C6 glioma cells, cell migration and invasion were significantly decreased in C6 glioma cells expressing miR-152-3p or miR-143-3p. These results suggest the possibility that miRNA produced by normal cells attenuates tumor progression through connexin 43-dependent and -independent mechanisms.