Tumor exosomes aggravate mitochondrial damage in myocardial ischemia/reperfusion injury
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE267761 | GEO | 2025/11/14
REPOSITORIES: GEO
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Project description:Most cancer-related deaths are caused by distant metastases, which are tumour cells that have escaped from a primary tumour and passed into the bloodstream to colonize a new organ. In this context, communication between tumour and stromal cells is essential. Indeed, tumor cells interact with cells in the tumor microenvironment and are able to modify them to their advantage. Both extracellular vesicles (EVs) and exosomes are heterogeneous populations of small vesicles present in the tumor microenvironment and in body fluids that have recently emerged as powerful mediators involved in this communication and their transport in fluids. Tumor cells release large quantities of exosomes containing tumor markers, which can then spread to distant locations.
The exosomes are of endosomal origin. They are composed of proteins, lipids, RNA and DNA, and they circulate in the bloodstream. They can be internalized by specific distant cells and thus deliver a functional message. It has recently been shown that tumor exosomes containing pro-metastatic factors form pre-metastatic niches, before the tumor cells actually arrive, while determining the metastatic organotropism of tumors. These properties are now opening up new avenues of research in tumor biomarkers. In recent years, several studies have highlighted different markers contained specifically in exosomes derived from cancer cells. Consequently, exosomes are considered as potential reservoirs of tumor biomarkers that could be clinically useful for the non-invasive diagnosis of cancer, with the advantage of being performed by liquid biopsy. The study of microRNA (miRNA) is of particular interest. Indeed, miRNAs are small non-coding RNAs (between 21 and 25 nucleotides) involved in the regulation of gene expression and which are frequently deregulated in cancer. Several studies underline that the variation of free miRNAs in the blood is correlated with the progression of the disease, particularly in colon cancer. However, the stability of free miRNAs is controversial. Therefore, exosomes represent a very advantageous means of transporting miRNAs in the blood, as they are able to protect miRNAs from degradation by RNAase.
The hypothesis of the project is that circulating exosomes derived from tumours contain markers including specific miRNAs that could be used as biomarkers of early prognosis (survival and progression), easily measured in blood samples from patients with colon cancer. But other molecules contained in exosomes could also be of interest.
| 2349603 | ecrin-mdr-crc
Project description:Although long thought to act cell autonomously, mutant KRAS colorectal cancer (CRC) cells release protein-laden exosomes that can alter the tumor microenvironment. We have previously shown that mutant KRAS induces EGFR-ligand trafficking to exosomes and drastically alters exosomal protein contents, leading to activities that contribute to neoplastic growth. We have performed small library RNAseq analysis on cells and matched exosomes from isogenic CRC cell lines differing only in KRAS status to determine whether mutant KRAS regulates the composition of secreted small RNAs. Exosomal small RNA profiles were distinct from cellular profiles, with principle component analysis showing clusters of mutant KRAS cell-derived exosomes distinct from wild type KRAS cell-derived exosomes. Secreted RNA species encompassed several different classes of small RNAs, including ribosomal and tRNA fragments, as well as mature miRNA sequences. miR-10b, was selectively increased in wild type KRAS-derived exosomes, whereas miR-100 was selectively increased in mutant KRAS-derived exosomes. Ceramide inhibition resulted in accumulation of miR-100 in mutant KRAS cells, suggesting KRAS-dependent miRNA export. In Transwell cell culture experiments, mutant, but not wild type, KRAS donor cells conferred miR-100-mediated target repression in wild type KRAS recipient cells miRNAseq deep sequencing for both cell and exosome mirnas of Dks-8, DLD-1, and DKO-1 cell lines. The DKs-8 line contains a wild type KRAS alleles, the DLD-1 line contains both wild type and mutant (G13D) KRAS alleles, and the DKO-1 line contains only a mutant KRAS allele.
2015-08-28 | E-GEOD-67004 | biostudies-arrayexpress
Project description:Breast milk is a complex liquid that enriched in immunological components and affect the development of the infant immune system. Exosomes, the membranous vesicles of endocytic origin, are ubiquitously in various body fluids which can mediate intercellular communication. MicroRNAs (miRNAs), a well-defined group of non-coding small RNAs, in human breast milk are packaged inside exosomes. Here, we present the identification of miRNAs in human breast milk exosomes using deep sequencing technology. We found that the immune-related miRNAs are enriched in breast milk exosomes, and are resistant to the general harsh conditions. Four small RNA libraries in human breast milk exosomes from four healthy women (30 +/- 0.9 years old, primiparity) when the infant were aged at 60 days were sequenced.
2011-12-21 | E-GEOD-32253 | biostudies-arrayexpress
Project description:Purpose: Analysis of exosomal miRNA in plasma of patients with metastatic and non-metastatic pancreatic cancer. To identify exosomes cargo specific miRNAs promoting cancer metastasis. Methods: We divide the plasma samples into five groups according to whether they have metastasis and undergo surgery.The five groups are Health(20),Metastasis Pre-operation and Post-operation (14),Non-metastasis Pre-operation and Post-operation(9).Then we collected the exosomes by ultracentrifugation and extracted the small RNA in each sample.Then, we analyzed the expression changes of miRNA by small RNA sequencing. Result: Different groups have different expression of small RNA. Compared with the non-metastatic group, the expression of miR-92a-3p , miR-148-3p and miR-25-3p increased in the metastatic group. Conclusion:Exosomal miRNA in pancreatic cancer patient derived plasma were analyze using Hiseq2500 sequencing technique. We identified that miR-92a-3p, miR-148-3p and miR-25-3p enriched in metastatic pancreatic cancer patient plasma derived exosomes.
2022-01-01 | GSE166799 | GEO
Project description:Background: Docosahexaenoic acid (DHA) is a natural compound with anticancer and anti-angiogenesis activity that is currently under investigation as both a preventative agent and an adjuvant to breast cancer therapy. However, the precise mechanisms of DHA’s anticancer activities are unclear. It is understood that the intercommunication between cancer cells and their microenvironment is essential to tumor angiogenesis. Exosomes are extracellular vesicles that are important mediators of intercellular communication and play a role in promoting angiogenesis. However, very little is known about the contribution of breast cancer exosomes to tumor angiogenesis or whether exosomes can mediate DHA’s anticancer action. Results: Exosomes were collected from MCF7 and MDA-MB-231 breast cancer cells after treatment with DHA. We observed an increase in exosome secretion and exosome microRNA contents from the DHA-treated cells. The expression of 83 microRNAs in the MCF7 exosomes was altered by DHA (>2-fold). The most abundant exosome microRNAs (let-7a, miR-23b, miR-27a/b, miR-21, let-7, and miR-320b) are known to have anti-cancer and/or anti-angiogenic activity. These microRNAs were also increased by DHA treatment in the exosomes from other breast cancer lines (MDA-MB-231, ZR751 and BT20), but not in exosomes from normal breast cells (MCF10A). When DHA-treated MCF7 cells were co-cultured with or their exosomes were directly applied to endothelial cell cultures, we observed an increase in the expression of these microRNAs in the endothelial cells. Furthermore, overexpression of miR-23b and miR-320b in endothelial cells decreased the expression of their pro-angiogenic target genes (PLAU, AMOTL1, NRP1 and ETS2) and significantly inhibited tube formation by endothelial cells, suggesting that the microRNAs transferred by exosomes mediate DHA’s anti-angiogenic action. These effects could be reversed by knockdown of the Rab GTPase, Rab27A, which controls exosome release. Conclusions: We conclude that DHA alters breast cancer exosome secretion and microRNA contents, which leads to the inhibition of angiogenesis. Our data demonstrate that breast cancer exosome signaling can be targeted to inhibit tumor angiogenesis and provide new insight into DHA’s anticancer action, further supporting its use in cancer therapy. Examination of small RNA populations in MCF7 cells and exosomes after DHA treatment.
2015-07-01 | E-GEOD-70432 | biostudies-arrayexpress
Project description:Breast milk is a complex liquid that enriched in immunological components and affect the development of the infant immune system. Exosomes, the membranous vesicles of endocytic origin, are ubiquitously in various body fluids which can mediate intercellular communication. MicroRNAs (miRNAs), a well-defined group of non-coding small RNAs, in human breast milk are packaged inside exosomes. Here, we present the identification of miRNAs in human breast milk exosomes using deep sequencing technology. We found that the immune-related miRNAs are enriched in breast milk exosomes, and are resistant to the general harsh conditions.
2011-12-21 | GSE32253 | GEO
Project description:Exosomes are small extracellular vesicles released through fusion of multivesicular bodies with the plasma membrane. The aim of this study was to investigate whether there are any differences in miRNAs in exosomes secreted from the prostate cancer cell line PC-3 and in parent cells, as well as to investigate whether there are any differences in miRNAs in cell lysates from PC-3 cells and the non-cancerous prostate cell line RWPE-1. Exosomes isolated from media of PC-3 cells, RNA isolated from exosomes and parent cells, as well as from RWPE-1 cells. Using 3 biological replicates, 1 replicate per array
2015-02-12 | E-GEOD-35813 | biostudies-arrayexpress
Project description:There is drastic racial disparities between Caucasian (CA) and African American (AA) for breast cancer. Circulating microRNAs exhibit stability and may serve as biomarkers in clinical settings. To discover potential microRNAs that mediate intercellular crosstalk and as biomarkers underlying the breast cancer racial disparity, serum exosomes from CA and AA were extracted and analyzed for its microRNA contents using small RNA sequencing.
2022-11-02 | GSE197809 | GEO
Project description:The goal of this study is to report that breast cancer associated exosomes contain microRNAs (miRNAs) associated with the RISC Loading Complex (RLC) and display cell-independent capacity to process precursor microRNAs (pre-miRNAs) into mature miRNAs. Pre-miRNAs, along with Dicer, AGO2, and TRBP, are present in exosomes of cancer cells. CD43 mediates the accumulation of Dicer specifically in cancer exosomes. Cancer exosomes mediate an efficient and rapid silencing of mRNAs to reprogram the target cell transcriptome. Exosomes derived from cells and sera of patients with breast cancer instigate non-tumorigenic epithelial cells to form tumors in a Dicer-dependent manner. These findings offer opportunities for the development of exosomes based biomarkers and therapies. Exosomes from cancer cells were isolated using established ultracentrifugation methods. The global miRNA content of non-tumorigenic cells was investigated before and after exosomes treatment to study the role of microRNA biogenesis in exosomes for cancer progression and the transformation process of normal cells.
2014-08-27 | E-GEOD-60713 | biostudies-arrayexpress
Project description:The goal of this study is to report that breast cancer associated exosomes contain microRNAs (miRNAs) associated with the RISC Loading Complex (RLC) and display cell-independent capacity to process precursor microRNAs (pre-miRNAs) into mature miRNAs. Pre-miRNAs, along with Dicer, AGO2, and TRBP, are present in exosomes of cancer cells. CD43 mediates the accumulation of Dicer specifically in cancer exosomes. Cancer exosomes mediate an efficient and rapid silencing of mRNAs to reprogram the target cell transcriptome. Exosomes derived from cells and sera of patients with breast cancer instigate non-tumorigenic epithelial cells to form tumors in a Dicer-dependent manner. These findings offer opportunities for the development of exosomes based biomarkers and therapies. Exosomes from cancer cells and non-tumorigenic cells were isolated using established ultracentrifugation methods. The global miRNA content of cancer exosomes and normosomes was investigated. Profiling of cells themselves was also used as a control. Exosomes with Dicer down regulation (MCF10AshDicer and MDA-MB-231shDicer exosomes), as well as MDA-MB-231 exosomes that contain a Dicer antibody inside were used to study the function Dicer protein in the microRNA biogenesis in exosomes.
2014-08-27 | E-GEOD-60714 | biostudies-arrayexpress