Functional microRNA is transferred between glioma cells.
Functional microRNA is transferred between glioma cells.
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DOI：
10.1158/0008-5472.can-10-0604
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发表时间：
2010-11-01
期刊：
影响因子：
11.2
通讯作者：
Chopp M
中科院分区：
文献类型：
--
作者：
Katakowski M;Buller B;Wang X;Rogers T;Chopp M
MicroRNA是单链的17-27个核苷酸的RNA分子，其通过靶mRNA的转录后沉默来调节基因表达。在这里，我们转化大鼠9 L胶质肉瘤细胞表达cel-miR-67，这是一种在大鼠中缺乏同源性的miRNA。将这些细胞与表达荧光素酶报告基因的细胞共培养，荧光素酶报告基因含有与cel-miR-67互补的序列，导致荧光素酶表达的显著抑制。在U87-MG人神经胶质瘤细胞系中也观察到这种效应。此外，通过向共培养物中添加甘珀酸来抑制荧光素酶抑制，表明间隙连接通讯调节microRNA的细胞间转移。最后，原位杂交揭示了与cel-miR-67表达细胞共培养后cel-miR-67缺失9 L细胞中cel-miR-67的存在。我们的数据表明，在胶质瘤细胞中转录的microRNA可以转移到相邻细胞，并诱导受体细胞中蛋白质表达的靶向抑制。这些发现揭示了脑肿瘤细胞之间靶向细胞间蛋白调节的新机制。
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.