Lung cancer exosomes initiate global long non-coding RNA changes in mesenchymal stem cells.

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.