Exosome-mediated miR-200a delivery into TGF-?-treated AGS cells abolished epithelial-mesenchymal transition with normalization of ZEB1, vimentin and Snail1 expression

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dc.authoridZarrabi, Ali/0000-0003-0391-1769
dc.authoridAshrafizadeh, Milad/0000-0001-6605-822X
dc.authoridKaramian, Amin/0000-0001-8853-2463
dc.authorwosidZarrabi, Ali/U-2602-2019
dc.authorwosidHashemi, Mehrdad/JHT-4661-2023
dc.authorwosidAshrafizadeh, Milad/JGC-9775-2023
dc.authorwosidMirzaei, Sepideh/AAB-1637-2022
dc.contributor.authorMirzaei, Sepideh
dc.contributor.authorGholami, Mohammad Hossein
dc.contributor.authorAghdaei, Hamid Asadzadeh
dc.contributor.authorHashemi, Mehrdad
dc.contributor.authorParivar, Kazem
dc.contributor.authorKaramian, Amin
dc.contributor.authorZarrabi, Ali
dc.date.accessioned2024-05-19T14:45:49Z
dc.date.available2024-05-19T14:45:49Z
dc.date.issued2023
dc.departmentİstinye Üniversitesien_US
dc.description.abstractExosomes are small extracellular vesicles that can be derived from human cells such as mesenchymal stem cells (MSCs). The size of exosomes is at nano-scale range and owing to their biocompatibility and other characteristics, they have been promising candidates for delivery of bioactive compounds and genetic materials in disease therapy, especially cancer therapy. Gastric cancer (GC) is a leading cause of death among patients and this malignant disease affects gastrointestinal tract that its invasiveness and abnormal migration mediate poor prognosis of patients. Metastasis is an increasing challenge in GC and microRNAs (miRNAs) are potential reg-ulators of metastasis and related molecular pathways, especially epithelial-to-mesenchymal transition (EMT). In the present study, our aim was to explore role of exosomes in miR-200a delivery for suppressing EMT-mediated GC metastasis. Exosomes were isolated from MSCs via size exclusion chromatography. The synthetic miR-200a mimics were transfected into exosomes via electroporation. AGS cell line exposed to TGF-beta for EMT induction and then, these cells cultured with miR-200a-loaded exosomes. The transwell assays performed to evaluate GC migration and expression levels of ZEB1, Snail1 and vimentin measured. Exosomes demonstrated loading effi-ciency of 5.92 +/- 4.6%. The TGF-beta treatment transformed AGS cells into fibroblast-like cells expressing two stemness markers, CD44 (45.28%) and CD133 (50.79%) and stimulated EMT. Exosomes induced a 14.89-fold increase in miR-200a expression in AGS cells. Mechanistically, miR-200a enhances E-cadherin levels (P < 0.01), while it decreases expression levels of beta-catenin (P < 0.05), vimentin (P < 0.01), ZEB1 (P < 0.0001) and Snail1 (P < 0.01), leading to EMT inhibition in GC cells. This pre-clinical experiment introduces a new strategy for miR-200a delivery that is of importance for preventing migration and invasion of GC cells.en_US
dc.description.sponsorshipIslamic Azad University, Science and Research. Branch, Tehran, Iranen_US
dc.description.sponsorshipThis article was a part of PhD thesis supported by Islamic Azad University, Science and Research. Branch, Tehran, Iran. The authors appreciate the help of laboratory managers in helping to perform this experiment.en_US
dc.identifier.doi10.1016/j.envres.2023.116115
dc.identifier.issn0013-9351
dc.identifier.issn1096-0953
dc.identifier.pmid37178752en_US
dc.identifier.scopus2-s2.0-85159208116en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org10.1016/j.envres.2023.116115
dc.identifier.urihttps://hdl.handle.net/20.500.12713/5359
dc.identifier.volume231en_US
dc.identifier.wosWOS:001002395200001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherAcademic Press Inc Elsevier Scienceen_US
dc.relation.ispartofEnvironmental Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmz20240519_kaen_US
dc.subjectMir-200aen_US
dc.subjectExosomeen_US
dc.subjectGastric Canceren_US
dc.subjectEmten_US
dc.subjectMetastasisen_US
dc.titleExosome-mediated miR-200a delivery into TGF-?-treated AGS cells abolished epithelial-mesenchymal transition with normalization of ZEB1, vimentin and Snail1 expressionen_US
dc.typeArticleen_US

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