Project description:To determine the different gene signatures between primary tumor and tumor-derived exosomes, we have employed RNA-sequencing as a discovery platform to identify gene signatures of tumor-derived exosomes, taking the original tumors as a control. We subcutaneously inoculated C57BL/6 mice with Lewis lung carcinoma (LLC). Three weeks later, tumor tissues were cut and tumor-derived exosomes were isolated as described in the "treatment protocol". Then, both exosomal RNA and tumor RNA were extracted and sequenced. From sequencing, we found that exosomal RNAs showed quite different transcript profiles from tumor RNAs. Examination of different gene signatures between primary tumor and tumor-derived exosomes. 2 replicates each.
Project description:To determine the different gene signatures between primary tumor and tumor-derived exosomes, we have employed RNA-sequencing as a discovery platform to identify gene signatures of tumor-derived exosomes, taking the original tumors as a control. We subcutaneously inoculated C57BL/6 mice with Lewis lung carcinoma (LLC). Three weeks later, tumor tissues were cut and tumor-derived exosomes were isolated as described in the "treatment protocol". Then, both exosomal RNA and tumor RNA were extracted and sequenced. From sequencing, we found that exosomal RNAs showed quite different transcript profiles from tumor RNAs.
Project description:Exosomes research has been strongly promoted by the discovery of different classes of RNAs, mainly miRNAs, which are transfered to target cells and modulate various simgnaling pathways in target cells. Inflamed endothelial cells derived exosomes, acting as carriers for intercellular information exchange in atherosclerosis, are worthy of further research to investigate the disease pathophysiological mechanisms. This study aimed to investigate the differentially microRNA expression between normal and inflamed endothelial cells derived exosomes.
Project description:MicroRNA has the potential for cross-regulation and functional integration of discrete biological processes during complex physiological events. In this study, we found that the highly expressed microRNAs in exosomes from bone marrow derived macrophage appear to control fibrotic healing response in the tendon. Notably, fibrotic microRNA-21 in mice distributed in the early stage of healing after tendon injury, having the similar expression with mammals. Therefore, we hypothesized the bone marrow derived macrophage secreted miRNAs-containing exosomes play important functions in peritendinous adhesion after tendon injury.
Project description:Cancer cell-derived vesicles, so-called exosomes, are important means in cell-cell communication between tumor cells and the tissue microenvironment. Amongst others, exosomes harbor functional RNAs, which are transferred to recipient cells and alter the cellular phenotype of respective cells. Aim of the current study was a detailed characterization of the RNA composition of cancer-cell derived exosomes in CLL. Due to prior results showing an enrichment of small RNAs in exosomes, this was focused on profiling of small RNAs. Further, the impact of high abundant exosomal RNAs in phenotypic alterations of cells in the tumor microenvironment upon exosome uptake was studied.
Project description:In this study, we isolated exosomes from liver cancer cell lines and exosomal miRNA expression was profiled by high-throughput sequencing to investigate the potential of exosomal contents as biomarkers for HCC.
Project description:In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed toward protumorigenic phenotypes, including the release of tumor-supportive cytokines and the expression of immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic skewing in CLL, we evaluated the role of tumor cell–derived exosomes in the cross-talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL-derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA species that is enriched in exosomes from plasma of CLL patients compared with healthy donor samples. Transfer of CLL-derived exosomes or hY4 alone to monocytes resulted in key CLL-associated phenotypes, including the release of cytokines, such as C-C motif chemokine ligand 2 (CCL2), CCL4, and interleukin-6, and the expression of PD-L1. These responses were abolished in Toll-like receptor 7 (TLR7)–deficient monocytes, suggesting exosomal hY4 as a driver of TLR7 signaling. Pharmacologic inhibition of endosomal TLR signaling resulted in a substantially reduced activation of monocytes in vitro and attenuated CLL development in vivo. Our results indicate that exosome-mediated transfer of noncoding RNAs to monocytes contributes to cancer-related inflammation and concurrent immune escape via PD-L1 expression.