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    Home > Active Ingredient News > Digestive System Information > Molecular Cancer: Exosome promotes the progression of colorectal cancer.

    Molecular Cancer: Exosome promotes the progression of colorectal cancer.

    • Last Update: 2020-08-11
    • Source: Internet
    • Author: User
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    Colorectal cancer (CRC) is one of the most common malignant tumors in the world and has a high risk of metastasis and recurrence.
    clinical results remain unsatisfactory, taking into account the shortcomings of traditional therapies, such as toxicity and poor tolerance.
    therefore, there is an urgent need to find sensitive CRC diagnostic biomarkers for early detection and to explore new CRC treatment targets.
    in recent years, the role of exosomes in cancer has attracted more and more attention.
    exosomes are lipid double-layer membrane bubbles with a diameter of about 30-100 nanometers secreted by different types of cells.
    increasing evidence that exosomes from tumor sources play a key role in tumor cell-to-cell communication through metastasis and exchange of carcinogenic molecules, including cycloRNA, microRNAs, mRNA, proteins, and lipids, and thus participate in tumor occurrence, tumor proliferation, tumor metastasis, angiogenesis, immunoflight, and drug resistance.
    ringRNA (circRNAs) is recognized as a member of the non-coding RNA (ncRNAs) family, with a closed-loop structure, with no 5 and 3 ends, and is closely related to the occurrence and development of cancer, including CRC.
    in addition, ring RNA is rich in exosomes and is critical for intercellular communication.
    reported that exosome cyclornaalle RNA is stable in the blood and may be a promising new biomarker for clinical testing.
    , MicroRNAs (miRNAs) is a class of endogenous 22-25 nt non-coding single-stranded RNA, a key regulatory factor for post-transcription gene regulation.
    ring RNA can be used as an effective miRNA sponge because they contain conservative miRNA target sites that competitively inhibit miRNAs to regulate the expression of downstream target genes.
    therefore, the authors speculate that exosome cyclornaalle RNA may be a new type of potential cancer treatment biomarker or treatment target.
    however, the function and potential mechanism of cancer-derived exosome cyclornarna is still largely unexplored.
    In this study, the authors first reported on the discovery of circPACRGL in the exosomes of tumor origin, and further explored its function and potential mechanism in CRC progression.
    found that circPACRGL enhances the proliferation, migration and invasion of CRC cells through miR-142-3p/miR-506-3p-TGF-271 axis, as well as the differentiation of N1-N2 neutrophils.
    therefore, the author's study reveals that circPACRGL plays a carcinogenic role in CRC cell survival and metastasis, providing a new theoretical basis for studying circRNAs' role in CRC treatment.
    previous studies have shown that cancer-derived exosomes are associated with tumor proliferation and metastasis.
    in order to explore the mechanism of exosomes in CRC, the authors isolated exosomes from the source of cancer cells from the two CRC cell lines of HCT116 and SW480.
    results found that the exosomes of CRC sources enhancecrcly proliferating, migrating and invasion of CRC.
    there have been reports of cyclornaalle RNA enrichment in exosomes of tumor sources.
    to identify CRC-related cyclornarnawrn, the authors analyzed the expression spectrum of HCT116 and SW480 cells (Ex-HCT116 and Ex-SW480) stimulated by tri-external prosthesis through RNA sequencing, as well as each untreated control group cell.
    found circPAGRAL (has_circ_0069313) to be the most expressed gene in the two previous groups.
    and further studies have found that circPACRGL in CRC cells increased significantly after the addition of tumor-derived exosomes.
    a lot of evidence that circRNA regulates as a miRNA sponge, mainly in cytoplasm.
    FISH fluorescence in situ hybridization (Fluorescence in situ hybridization, FISH) results show that circPACRGL transcription signals are mainly distributed in the cytoplasm of HCT116 and SW480 cells, but have a small amount of hybridization signals in the nucleus.
    To study the miRNAs that may be associated with circPACRGL, the authors used the online bioinformatics database StarBase 2.0 (http://starbase.sysu.edu.cn/) and introduced miRNAs that are most likely to complement each other.
    in these predicted targetmirnas, the authors found that circPACRGL has both miR-142-3p and miR-506-3p junctions.
    double luciferase reporting genetic experiments further confirmed that miR-142-3p and miR-506-3p are targets for circPACRGL.
    MiRNAs can be combined with three UTR genes that regulate mRNA and protein expression.
    use the online bioinformatics tool StarBase 2.0 (http://starbase.sysu.edu.cn/) to predict the target genes of miR-142-3p and miR-506-3p.
    the authors found that TGF-beta 1 was one of the best candidates.
    reported that TGF-beta 1 is involved in tumor development and is associated with the differentiation of N1/N2 neutrophils.
    in order to assess the effects of miR-142-3p and miR-506-3p on TGF-cad1 expression, the authors conducted a listofinase report gene test, confirming that TGF-cad1 is a common target gene for miR-142-3p and miR-506-3p. based on the above data,
    speculated that circPACRGL may regulate the proliferation, migration and invasion of CRC by miR-142-3p/miR-506-3p-TGF-beta-1 axis.
    CCK8 results showed that CRC cell proliferation was significantly improved in the CRC exosome treatment (Ex-HCT116) group compared with the control group.
    , lowering the circPACRGL significantly reduces the proliferation of CRC cells compared to the ExHCT116 group, which decreases the inhibition after the expression of miR-142-3p/miR-506-3p processing or TGF-tGF-. similar effects have been observed in
    in apoptosis.
    flow cytometer test showed that the proportion of apoptotic cells in exosome-stimulated CRC cells was effectively reduced compared with the control group.
    in general, the data show that circPACRGL promotes CRC proliferation, migration and invasion by regulating the miR-142-3p/miR-506-3p-TGF-beta-1 axis.
    overall, the data from this study are the first to demonstrate that circPACRGL plays a cancer-promoting role in CRC development through the miR-142-3p/miR-506-3p-TGF-beta-1 axis, which helps us to better understand circRNAs' mechanisms in CRC progression and provides a promising biomarker for CRC treatment.
    , however, the authors did not examine the effects of circPACRGL-miR-142-3p/miR-506-3p-TGF-beta-1 axis after exosome therapy in CRC patient samples.
    the future, the focus will be on the effects of tumor-derived exosome circPACRGL on CRC.
    study of circPACRGL's clinical application in CRC treatment will be more accurate and meaningful.
    study suggests that prevention of circPACRGL/miR-142-3p/miR-506-3p-TGF-beta 1 axis is a promising CRC treatment strategy.
    .
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