Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes
Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes
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DOI：
10.1002/cbin.10301
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发表时间：
2014-09-01
影响因子：
3.9
通讯作者：
Dalay, Nejat
中科院分区：
文献类型：
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作者：
Gezer, Ugur;Ozgur, Emre;Dalay, Nejat
长链非编码RNA（lncRNA）参与调节染色质修饰、基因转录、mRNA翻译和蛋白质功能。我们最近报道了一组lncRNA在HeLa和MCF-7细胞中的基础表达水平的高度变化及其对DNA损伤诱导的差异反应。在这里，我们假设具有不同细胞表达的lncRNA分子在分泌的外泌体中可能具有差异丰度，并且它们的外泌体水平将反映细胞对DNA损伤的反应。对培养细胞分泌的外泌体中的MALAT 1、HOTAIR、lincRNA-p21、GAS 5、TUG 1、CCND 1-ncRNA进行了表征。与细胞相比，在外来体中观察到lncRNA的不同表达模式。具有相对低表达水平的RNA分子（lincRNA-p21、HOTAIR、ncRNA-CCND 1）在外来体中高度富集。TUG 1和GAS 5水平在外来体中适度升高，而MALAT 1-细胞中最丰富的分子-以与其细胞水平相当的水平存在。lincRNA-p21和ncRNA-CCND 1是主要分子;它们的外泌体水平最好地反映了细胞暴露于博来霉素诱导的DNA损伤后它们的细胞水平的变化。总之，我们提供的证据表明，lncRNA在外来体中具有差异丰度，表明选择性加载。
Long non-coding RNAs (lncRNAs) are involved in regulating chromatin modifications, gene transcription, mRNA translation, and protein function. We recently reported a high variation in the basal expression levels of a panel of lncRNAs in HeLa and MCF-7 cells and their differential response to DNA damage induction. Here, we hypothesized that lncRNA molecules with different cellular expression may have a differential abundance in secreted exosomes, and their exosome levels would reflect cellular response to DNA damage. MALAT1, HOTAIR, lincRNA-p21, GAS5, TUG1, CCND1-ncRNA in exosomes secreted from cultured cells were characterized. A different expression pattern of lncRNAs in exosomes was seen compared to cells. RNA molecules with relative low expression levels (lincRNA-p21, HOTAIR, ncRNA-CCND1) were highly enriched in exosomes. TUG1 and GAS5 levels were moderately elevated in exosomes, whereas MALAT1-which was the most abundant molecule in cells-was present at levels comparable to its cellular levels. lincRNA-p21 and ncRNA-CCND1 were the main molecules; exosome levels of them best reflect the change of their cellular levels upon exposure of the cells to bleomycin-induced DNA damage. In conclusion, we provide evidence that lncRNAs have a differential abundance in exosomes, indicating a selective loading.