Project description:Exosomes play important roles in intercellular communication through the delivery of their cargoes, which include proteins, lipids, and RNAs. Increasingly, multiple studies have reported the association between exosomal small non-coding RNAs and cancer, due to their regulatory functions in gene expression. Hence, analysis of the features of small non-coding RNA expression and their incorporation into exosomes is important for cancer research. Here, we performed deep sequencing to investigate the expression of small RNAs in plasma exosomes from lung adenocarcinoma patients, lung squamous cell carcinoma patients, and healthy controls. We found that 5’ YRNA hY4-derived fragments are significantly upregulated in non-small cell lung cancer (NSCLC) exosomes, and may serve as a novel class of circulating biomarkers for NSCLC diagnosis. We also identified that the RNY4P7 gene on chromosome 2 may not be a pseudogene, because the corresponding transcript hY4 reverse fragment was detected in exosomes and cells. Further, we demonstrated that a panel of small RNAs, including miR-451a and miR-122-5p, may be selectively sorted into NSCLC exosomes. Overall, our studies have indicated a wider range of biological effects in NSCLC that may be mediated by exosomal small RNAs than previously known.
Project description:Prostate cancer is one of the major cancers that seriously affect men's health. The low specificity of prostate-specific antigen (PSA) for prostate cancer has resulted in the overdiagnosis and subsequent overtreatment of clinically indolent tumors. There is an urgent need for noninvasive and easy diagnostic assays to help evaluate whether a prostate biopsy is warranted. Many non-coding RNAs (eg, microRNAs, long non-coding RNAs, circular RNAs) have been reported to play key roles in prostate cancer progression, showing great potential to impact cancer diagnostics and therapies. Remarkably, exosomes secreted by cells into body fluids contain molecules that reflect the disease information, and urinary exosomes could be used to detect prostate cancer as a new type of liquid biopsies. Non-coding RNAs are enriched and stable in exosomes. We performed high-throughput sequencing on urine-derived exosomes of 11 patients with high-grade (Gleason score 7 or greater) prostate cancer and 11 patients with benign prostatic hyperplasia to screen differentially expressed non-coding RNAs.
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:Hypoxia is a common feature of solid tumors and is associated with aggressiveness and poor prognosis of patients. Exosomes are involved in mediating cellular environment interactions. circRNAs are a class of non-coding RNAs (ncRNAs) broadly expressed in cells and exosomes. However, in lung adenocarcinoma tumor development, functions and regulatory mechanisms of exosomal circ-RNAs induced by hypoxia remain poorly understood.To further explore the differences in recombinant RNA expression in hypoxic and normoxic exosomes derived from lung adenocarcinoma cell line
2023-01-21 | GSE144053 | GEO
Project description:Analysis of long non-coding RNAs in Aila induced non-small cell lung cancer inhibition
Project description:Studies have shown that IH may promote the development of non-small-cell lung cancer (NSCLC), Exosomes carry specific proteins, lipids, small molecule RNAs (miRNAs) as well as other bioactive substances, which play an important role in tumor growth. The role of exosomal miRNAs in the promotion of tumor development by IH has not been studied.
Project description:Type 1 diabetes (T1D) is characterized by immune mediated destruction of insulin producing β cells. Biomarkers capable of identifying T1D risk and dissecting disease-related heterogeneity represent an unmet clinical need. Aims: Towards the goal of informing T1D biomarker strategies, we profiled different classes of RNAs in human islet-derived exosomes and identified RNAs that were differentially expressed under cytokine stress conditions. Human pancreatic islets were obtained from cadaveric donors and treated with/without IL-1β and IFN-γ to mimic the pro-inflammatory T1D milieu. Total RNA and small RNA sequencing were performed to identify long (mRNA and long non-coding RNAs) and different classes of small non-coding RNAs. RNAs with fold change ≥ 1.3 and p-value < 0.05 were considered as differentially expressed. mRNAs and miRNAs species represented the most abundant long and small RNA species, respectively. Expression patterns of each class of RNA were changed with cytokine treatment. Differentially expressed long RNAs and targets of small non-coding RNAs were predicted to be involved in insulin secretion, calcium signaling, necrosis and apoptosis. Our data provides the first comprehensive catalog of protein coding and non-coding RNAs in human islet-derived exosomes and identifies RNAs that are dysregulated under cytokine stress.
Project description:Type 1 diabetes (T1D) is characterized by immune mediated destruction of insulin producing β cells. Biomarkers capable of identifying T1D risk and dissecting disease-related heterogeneity represent an unmet clinical need. Aims: Towards the goal of informing T1D biomarker strategies, we profiled different classes of RNAs in human islet-derived exosomes and identified RNAs that were differentially expressed under cytokine stress conditions. Human pancreatic islets were obtained from cadaveric donors and treated with/without IL-1β and IFN-γ to mimic the pro-inflammatory T1D milieu. Total RNA and small RNA sequencing were performed to identify long (mRNA and long non-coding RNAs) and different classes of small non-coding RNAs. RNAs with fold change ≥ 1.3 and p-value < 0.05 were considered as differentially expressed. mRNAs and miRNAs species represented the most abundant long and small RNA species, respectively. Expression patterns of each class of RNA were changed with cytokine treatment. Differentially expressed long RNAs and targets of small non-coding RNAs were predicted to be involved in insulin secretion, calcium signaling, necrosis and apoptosis. Our data provides the first comprehensive catalog of protein coding and non-coding RNAs in human islet-derived exosomes and identifies RNAs that are dysregulated under cytokine stress.
Project description:Translational rate has been deregulated in many cancers through small non-coding RNAs aberrations. Herein we focus on miRNAs, tRNAs and tRFs paterns in lung cancer biopsies.
Project description:The base excision repair (BER) Apurinic/apyrimidinic endonuclease 1 (APE1) enzyme is endowed with several non-repair activities, such as the cell response to genotoxic stress, the regulation of gene expression and miRNAs processing. We recently demonstrated that APE1 can be actively secreted by mammalian cells through exosomes. The role of APE1 in exosomes is still unknown, especially regarding the molecular mechanism involving small non-coding RNAs vesicular secretion. miRNAs loading into exosomes is a regulated and selective process, since not all the expressed miRNAs are indistinctly conveyed into exosomes. Through a dedicated transcriptomic analysis on cellular and vesicular small RNAs, we identified secreted miRNAs characterized by enriched sequence motifs and possible binding sites for APE1. In 50 out of 53 DE-miRNA precursors, we surprisingly found EXO motifs and proved that APE1 cooperates with hnRNPA2B1 for the EV-sorting of a subsets of miRNAs, including miR-1246, through a direct binding to GGAG stretch. We provide evidence of a new post-transcriptional role for this ubiquitous DNA-repair enzyme towards miRNAs secretion mechanisms, that could be exploited to interfere with tumor microenvironment.