Wang Shihua, Li Xiaoxia, Zhu Rongjia, Han Qin, Zhao Robert Chunhua
Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing 100005, P.R. China.
Int J Oncol. 2016 Feb;48(2):681-9. doi: 10.3892/ijo.2015.3272. Epub 2015 Nov 27.
Mesenchymal stem cells (MSCs) can be attracted to tumor sites and become an important component of the tumor microenvironment, thus contributing to tumor development. Emerging evidence suggests that tumor cells could transfer genetic information into MSCs through the release of exosomes. However, the molecular mechanisms by which tumor exosomes contribute to interactions between MSCs and tumor cells remain largely unknown. In this study, we found that lung tumor cell derived exosomes could inhibit MSCs osteogenic and adipogenic differentiation. We then investigated the involvement of long non-coding RNAs, a new class of regulators, in tumor exosome treated MSCs by a comprehensive lncRNA and mRNA profiling. lncRNAs (9.1%) (2775 out of 30586) and 9.3% of protein-coding mRNA (2439 out of 26109) were differentially expressed (fold-change ≥2; P-value ≤0.05) in lung tumor cell exosome treated MSCs. Furthermore, we characterized the differentially expressed lncRNAs through their classes and length distribution and correlated them with differentially expressed mRNA. Noteworthy, GO analysis of biological process showed that upregulated mRNAs were enriched in mRNA metabolic process, while downregulated ones were enriched in detection of mechanical stimulus involved in sensory perception. Pathway analysis indicated that 32 pathways were upregulated while 7 were downregulated in A549 exosome treated MSCs. Here, we are the first to determine genome-wide lncRNA expression patterns in exosome treated MSCs by microarray and the results will bring new insights into the mechanisms underlying interactions between tumor cells exosomes and its environmental component the MSCs.
间充质干细胞（MSCs）可被吸引至肿瘤部位，并成为肿瘤微环境的重要组成部分，从而促进肿瘤发展。新出现的证据表明，肿瘤细胞可通过释放外泌体将遗传信息传递给MSCs。然而，肿瘤外泌体促进MSCs与肿瘤细胞相互作用的分子机制仍 largely unknown。在本研究中，我们发现肺癌细胞衍生的外泌体可抑制MSCs的成骨和成脂分化。然后，我们通过全面的lncRNA和mRNA谱分析，研究了一类新的调节因子——长链非编码RNA（lncRNAs）在肿瘤外泌体处理的MSCs中的作用。在肺癌细胞外泌体处理的MSCs中，lncRNAs（9.1%）（30586个中的2775个）和9.3%的蛋白质编码mRNA（26109个中的2439个）差异表达（变化倍数≥2；P值≤0.05）。此外，我们通过其类别和长度分布对差异表达的lncRNAs进行了表征，并将它们与差异表达的mRNA相关联。值得注意的是，生物过程的GO分析表明，上调的mRNA在mRNA代谢过程中富集，而下调的mRNA在感觉感知中涉及的机械刺激检测中富集。通路分析表明，在A549外泌体处理的MSCs中，32条通路上调，7条通路下调。在这里，我们首次通过微阵列确定了外泌体处理的MSCs中的全基因组lncRNA表达模式，结果将为肿瘤细胞外泌体与其环境成分MSCs之间相互作用的潜在机制带来新的见解。
