MicroRNA profiling of brain metastasis competent cell-derived exosomes
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Camacho L
PROVIDER: S-ECPF-GEOD-48934 | biostudies-other | 2013
REPOSITORIES: biostudies-other
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Project description:Exosomes are small membrane vesicles released by most cell types including tumor cells. The intercellular exchange of proteins and genetic material via exosomes is a potentially effective approach for cell-to-cell communication and it may perform multiple functions aiding to tumor survival and metastasis. We investigated microRNA and protein profiles of brain metastatic (BM) versus non-brain metastatic (non-BM) cell-derived exosomes. We studied the cargo of exosomes isolated from brain-tropic 70W, MDA-MB-231BR, and circulating tumor cell brain metastasis-selected markers (CTC1BMSM) variants, and compared them with parental non-BM MeWo, MDA-MB-231P and CTC1P cells, respectively. By performing microRNA PCR array we identified one up-regulated (miR-210) and two down-regulated miRNAs (miR-19a and miR-29c) in BM versus non-BM exosomes. Second, we analyzed the proteomic content of cells and exosomes isolated from these six cell lines, and detected high expression of proteins implicated in cell communication, cell cycle, and in key cancer invasion and metastasis pathways. Third, we show that BM cell-derived exosomes can be internalized by non-BM cells and that they effectively transport their cargo into cells, resulting in increased cell adhesive and invasive potencies. These results provide a strong rationale for additional investigations of exosomal proteins and miRNAs towards more profound understandings of exosome roles in brain metastasis biogenesis, and for the discovery and application of non-invasive biomarkers for new therapies combating brain metastasis.
| S-EPMC3774795 | biostudies-literature
Project description:Objective of this work was to characterize the miRNA profile of exosomes isolated from brain-homing cell lines (MDA-MB-231BR, CTC1BMSM, and 70W) with their respective parental non-brain metastatic cell lines (MDA-MB-231P, CTC1P and MeWo). Exosomes derived from the six cell lines were isolated. Brain metastatic cell-derived exosomal miRNAs were compared with non brain metastatic cell lines (MDA-MB-231BR versus MDA-MB-231P, CTC1BMSM versus CTC1P, and 70W versus MeWo).
2013-07-16 | E-GEOD-48934 | biostudies-arrayexpress
Project description:Objective of this work was to characterize the miRNA profile of exosomes isolated from brain-homing cell lines (MDA-MB-231BR, CTC1BMSM, and 70W) with their respective parental non-brain metastatic cell lines (MDA-MB-231P, CTC1P and MeWo).
2013-07-16 | GSE48934 | GEO
Project description:PurposeTo elucidate the microRNAs existent in exosomes derived from stored red blood cell (RBC) unit and their potential function.Materials and methodsExosomes were isolated from the supernatant derived from stored RBC units by sequential centrifugation. Isolated exosomes were characterized by TEM (transmission electron microscopy), western blotting, and DLS (dynamic light scattering). MicroRNA (miRNA) microarray was performed to detect the expression of miRNAs in 3 exosome samples. Results revealed miRNAs that were simultaneously expressed in the 3 exosome samples and were previously reported to exist in mature RBCs. Functions and potential pathways of some detected miRNAs were illustrated by bioinformatic analysis. Validation of the top 3 abundant miRNAs was carried out by qRT-PCR (quantitative reverse transcription-polymerase chain reaction).ResultsTEM and DLS revealed the mean size of the exosomes (RBC-derived) as 64.08 nm. These exosomes exhibited higher abundance of short RNA than the long RNA. 78 miRNAs were simultaneously detected in 3 exosome samples and mature RBCs. Several biological processes might be impacted by these miRNAs, through their target gene(s) enriched in a particular signalling pathway. The top 3 (abundant) miRNAs detected were as follows: miR-125b-5p, miR-4454, and miR-451a. qRT-PCR revealed higher abundance of miR-451a than others. Only miR-4454 and miR-451a abundance tended to increase with increasing storage time.ConclusionExosomes derived from stored RBC units possessed multiple miRNAs and, hence, could serve various functions. The function of exosomes (RBC-derived) might be implemented partly by the predominantly enriched miR-451a.
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Project description:Cell-derived exosomes are leading candidates for in vivo drug delivery carriers. In particular, exosomes derived from 293T cells are used most frequently, although exosome dosing has varied greatly among studies. Considering their biological origin, it is crucial to characterize the molecular composition of exosomes if large doses are to be administered in clinical settings. In this study, we present the first comprehensive analysis of the protein, messenger RNA and microRNA profiles of 293T cell-derived exosomes; then, we characterized these data using Gene Ontology annotation and Kyoto Encyclopedia for Genes and Genomes pathway analysis. Our study will provide the basis for the selection of 293T cell-derived exosome drug delivery systems. Profiling the exosomal signatures of 293T cells will lead to a better understanding of 293T exosome biology and will aid in the identification of any harmful factors in exosomes that could cause adverse clinical effects.
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Project description:Cancer stem-like cells (CSCs) have been identified as the initial cell in formation of cancer. Quiescent CSCs can "hide out" from traditional cancer therapy which may produce an initial response but are often unsuccessful in curing patients. Thus, levels of CSC in patients may be used as an indicator to measure the chance of recurrence of cancer after therapy. The goals of our work are to develop specific exosomal miRNA clusters for gastric CSCs that can potentially predict which patients are at high risk for developing gastric cancer (GC) in order to diagnose GC at an early stage. Here, upon sorting gastric CSCs, we initially isolated and characterized exosomes secreted by both gastric CSCs and their differentiated cells (DCs). By deep sequencing of each exosomal miRNA library, 11 typical differentially expressed miRNAs were identified as signature miRNAs for CSC. Gene target prediction, GO annotation and KEGG pathway enrichment analysis showed possible functions associated with these signature miRNAs. Hence, upon research of exosomal miRNAs that would influence behavior of tumor cells and their microenvironment, this study shows that a specific miRNA signature is present in CSCs, and implies that a potential miRNA biomarker reflecting the stage of gastric cancer progression and metastasis could be developed in the foreseeable future.
| S-EPMC5706839 | biostudies-literature
Project description:Bovine milk is rich in exosomes, which contain abundant miRNAs and play important roles in the regulation of neonatal growth and development of adaptive immunity. Here, we analyzed miRNA expression profiles of bovine milk exosomes from three healthy and three mastitic cows, and then six miRNA libraries were constructed. Interestingly, we detected no scRNAs and few snRNAs in milk exosomes; this result indicated a potential preference for RNA packaging in milk exosomes. A total of 492 known and 980 novel exosomal miRNAs were detected, and the 10 most expressed miRNAs in the six samples accounted for 80-90% of total miRNA-associated reads. Expression analyses identified 18 miRNAs with significantly different expression between healthy and infected animals; the predicted target genes of differentially expressed miRNAs were significantly enriched in immune system process, response to stimulus, growth, etc. Moreover, target genes were significantly enriched in several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including inflammatory, immune, and cancer pathways. Our survey provided comprehensive information about milk exosomes and exosomal miRNAs involved in mastitis. Moreover, the differentially expressed miRNAs, especially miR-223 and miR-142-5p, could be considered as potential candidates for mastitis.
| S-EPMC6045547 | biostudies-literature
Project description:BackgroundThe mesenchymal stem cells (MSCs) have enormous therapeutic potential owing to their multi-lineage differentiation and self-renewal properties. MSCs express growth factors, cytokines, chemokines, and non-coding regulatory RNAs with immunosuppressive, anti-tumor, and migratory properties. MSCs also release several anti-cancer molecules via extracellular vesicles, that act as pro-apoptotic/tumor suppressor factors. This study aimed to identify the stem cell-derived secretome that could exhibit anti-cancer properties through molecular profiling of cargos in MSC-derived exosomes.MethodsHuman umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from umbilical cord tissues and culture expanded. Subsequently, exosomes were isolated from hUCMSC conditioned medium and characterized by DLS, electron microscopy. Western blot for exosome surface marker protein CD63 expression was performed. The miRNA profiling of hUCMSCs and hUCMSC-derived exosomes was performed, followed by functional enrichment analysis.ResultsThe tri-lineage differentiation potential, fibroblastic morphology, and strong expression of pluripotency genes indicated that isolated fibroblasts are MSCs. The isolated extracellular vesicles were 133.8 ± 42.49 nm in diameter, monodispersed, and strongly expressed the exosome surface marker protein CD63. The miRNA expression profile and gene ontology (GO) depicted the differential expression patterns of high and less-expressed miRNAs that are crucial to be involved in the regulation of apoptosis. The LCMS/MS data and GO analysis indicate that hUCMSC secretomes are involved in several oncogenic and inflammatory signaling cascades.ConclusionPrimary human MSCs released miRNAs and growth factors via exosomes that are increasingly implicated in intercellular communications, and hUCMSC-exosomal miRNAs have a critical influence in regulating cell death and apoptosis of cancer cells.
| S-EPMC9478013 | biostudies-literature
Project description:BackgroundMetastases within liver or the brain are the most common causes of mortality from lung cancer (LC). Predicting liver or brain metastases before having evidence from imaging of the tumors is challenging but important for early patient intervention. According to mounting evidence, exosomes circulating within blood may facilitate cancer spread by transporting certain proteins for target cells.MethodsUsing liquid chromatography-MS/MS, we investigated the plasma exosomes' proteomic profiles derived from 42 metastatic LC patients [16 solitary liver metastasis (LM), together with 26 solitary brain metastasis (BM)] and 25 local advanced (LA) lung cancer cases without metastasis, together with five healthy controls (HC), assessing the LM and BM pathogenesis and find potential novel organ-designated proteomic biomarkers. Using ELISA assay, we verified the expression levels of three plasma exosomal protein biomarkers in 110 LC patients, including 40 solitary LM, 32 solitary BM and 38 LA, and 25 HC.ResultsIn total, 143 and 120 differentially expressed exosome-based proteins (DEEPs) were found to be dysregulated in LM and BM of lung cancer (LM-DEEPs, BM-DEEPs), compared for LA lung cancer samples, respectively. The bioinformatics analyses indicated the heterogeneity and homogeneity in LM-DEEPs and BM-DEEPs. They were primarily engaged within proteomic triggering cascade, ECM-receptor interaction, and the collagen-containing extracellular matrix. Regarding heterogeneity, LM-DEEPs primarily consisted of proteoglycans, lipoprotein, integrin, and heat shock protein, whereas the BM-DEEPs consisted of calcium-dependent/S100 proteins. Furthermore, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)-plasma-stemming exosome proteomics showed heterogeneity, which helped to explain some of the differences between SCLC and NSCLC's metastatic features. We also found that SELL and MUC5B could be used as diagnostic markers of BM, while APOH, CD81, and CCT5 could help diagnose LM in LC patients. Additionally, we demonstrated in a validation cohort that MUC5B and SELL could serve as biomarkers for diagnosing BM, and APOH could be a novel potential diagnostic biomarker of LM.ConclusionWe presented the comprehensive and comparative plasma-stemming exosomes' proteomic profiles from cases of LC who had isolated liver and brain metastases for the first time. We also suggested several possible biomarkers and pathogenic pathways that might be a great starting point for future research on LC metastasis.
| S-EPMC10540327 | biostudies-literature
Project description:ObjectiveBone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) could mediate the malignancy of tumor cells by transmitting targeted cargo. Therein, this study intends to explore the function of BMSC-Exos transmitting microRNA-425 (miR-425)/cytoplasmic polyadenylation binding protein 1 (CPEB1) in lung cancer growth.MethodsmiR-425 and CPEB1 levels in cancer tissues and cells were measured. BMSCs and their exosomes were collected and identified. After intervention with BMSC-Exos, miR-425 or CPEB1, invasion and migration of A549 and NCI-H1299 cells in vitro, and lung metastasis of A549 cells in vivo were observed. The relationship between miR-425 and CPEB1 was verified.ResultsmiR-425 was highly expressed while CPEB1 was lowly expressed in lung cancer tissues of patients. CPEB1 was the direct target of miR-425. Down-regulating miR-425 or up-regulating CPEB1 decreased cell invasion and migration ability of A549 and NCI-H1299 cells, as well as decreased the number of lung metastasis lesions in vivo. After co-culture with BMSC-Exos, A549 and NCI-H1299 cells showed promoted migration and invasion in vitro and A549 cells demonstrated increased lung metastasis in vivo. Down-regulated miR-425 or up-regulated CPEB1 reversed the promotion of BMSC-Exos on lung cancer cell invasion, migration and lung metastasis.ConclusionBMSC-Exos could deliver miR-425 to inhibit CPEB1 expression in lung cancer cells, thereby promoting the malignant biological properties of lung cancer cells and their metastasis in vivo.
| S-EPMC9061616 | biostudies-literature