Identifying mRNA, microRNA and protein profiles of melanoma exosomes.
Identifying mRNA, microRNA and protein profiles of melanoma exosomes.
复制标题
DOI：
10.1371/journal.pone.0046874
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
McMasters KM
中科院分区：
文献类型：
--
作者：
Xiao D;Ohlendorf J;Chen Y;Taylor DD;Rai SN;Waigel S;Zacharias W;Hao H;McMasters KM
外来体是由多种细胞类型（包括肿瘤细胞）和在各种疾病状况下分泌到体液中的小膜囊泡。肿瘤外泌体含有完整和功能性mRNA、小RNA（包括miRNA）和可以改变细胞环境以有利于肿瘤生长的蛋白质。分子分析可以增加我们对外泌体在黑色素瘤进展中的作用的理解，并可能导致发现有用的生物标志物。在本研究中，我们使用mRNA阵列分析来鉴定数千种与黑色素瘤进展和转移相关的外泌体mRNA。类似地，miRNA阵列分析鉴定了参与黑色素瘤侵袭的特定miRNA，如hsa-miR-31、-185和-34b。我们还使用了蛋白质组学分析，发现了差异表达的黑色素瘤外泌体蛋白，包括HAPLN 1，GRP 78，syntenin-1，annexin A1和annexin A2。重要的是，正常黑素细胞通过黑色素瘤细胞来源的外泌体中转运的分子获得侵袭能力。我们的研究结果表明，与正常黑素细胞的外泌体相比，黑色素瘤来源的外泌体具有独特的基因表达特征，miRNA和蛋白质组学特征。据我们所知，这是首次深入筛选黑色素瘤外泌体中的全转录组/miRNome/蛋白质组表达。这些结果为未来更深入地研究肿瘤来源的黑色素瘤外泌体提供了一个起点，这将有助于我们了解黑色素瘤的生物发生和可能转化为临床应用或作为黑色素瘤非侵入性生物标志物的新药物靶点。
Exosomes are small membranous vesicles secreted into body fluids by multiple cell types, including tumor cells, and in various disease conditions. Tumor exosomes contain intact and functional mRNAs, small RNAs (including miRNAs), and proteins that can alter the cellular environment to favor tumor growth. Molecular profiling may increase our understanding of the role of exosomes in melanoma progression and may lead to discovery of useful biomarkers. In the present study, we used mRNA array profiling to identify thousands of exosomal mRNAs associated with melanoma progression and metastasis. Similarly, miRNA array profiling identified specific miRNAs, such as hsa-miR-31, -185, and -34b, involved in melanoma invasion. We also used proteomic analysis and discovered differentially expressed melanoma exosomal proteins, including HAPLN1, GRP78, syntenin-1, annexin A1, and annexin A2. Importantly, normal melanocytes acquired invasion ability through molecules transported in melanoma cell-derived exosomes. Our results indicate that melanoma-derived exosomes have unique gene expression signatures, miRNA and proteomics profiles compared to exosomes from normal melanocytes. To the best of our knowledge, this is the first in-depth screening of the whole transcriptome/miRNome/proteome expression in melanoma exosomes. These results provide a starting point for future more in-depth studies of tumor-derived melanoma exosomes, which will aid our understanding of melanoma biogenesis and new drug-targets that may be translated into clinical applications, or as non-invasive biomarkers for melanoma.