MicroRNAs are single-stranded 17-27 nucleotide RNA molecules that regulate gene expression by post-transcriptional silencing of target mRNAs. Here, we transformed rat 9L gliosarcoma cells to express cel-miR-67, a miRNA that lacks homology in rat. Co-culture of these cells with cells that expressed a luciferase reporter, which contained a complementary sequence to cel-miR-67, resulted in significant suppression of luciferase expression. This effect was also observed in the U87-MG human glioma cell line. Moreover, luciferase suppression was inhibited by the addition of carbenoxolone to co-cultures, suggesting that gap junction communication regulates intercellular transfer of microRNA. Finally, in situ hybridization revealed the presence of cel-miR-67 in cel-miR-67 null 9L cells after co-culture with cel-miR-67 expressing cells. Our data demonstrate that microRNA transcribed in glioma cells can be transferred to adjacent cells and induces targeted inhibition of protein expression in the acceptor cells. These findings reveal a novel mechanism of targeted intercellular protein regulation between brain tumor cells.

PMID: 20841486 [PubMed - as supplied by publisher] Source: National Library of Medicine.