MiR-29a-laden extracellular vesicles efficiently induced apoptosis through autophagy blockage in HCC cells

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dc.authorscopusidAli Zarrabi / 23483174100
dc.authorwosidAli Zarrabi / GSA-3718-2022
dc.contributor.authorSeydi, Homeyra
dc.contributor.authorNouri, Kosar
dc.contributor.authorShokouhian, Bahare
dc.contributor.authorPiryaei, Abbas
dc.contributor.authorHassan, Moustapha
dc.contributor.authorCordani, Marco
dc.contributor.authorZarrabi, Ali
dc.contributor.authorShekari, Faezeh
dc.contributor.authorVosough, Massoud
dc.date.accessioned2025-04-18T10:01:37Z
dc.date.available2025-04-18T10:01:37Z
dc.date.issued2024
dc.departmentİstinye Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Biyomedikal Mühendisliği Bölümü
dc.description.abstractBackground: In spite of significant advancements in theraputic modalities for hepatocellular carcinoma (HCC), there is still a high annual mortality rate with a rising incidence. Major challenges in the HCC clinical managment are related to the development of therapy resistance, and evasion of tumor cells apoptosis which leading unsatisfactory outcomes in HCC patients. Previous investigations have shown that autophagy plays crucial role in contributing to drug resistance development in HCC. Although, miR-29a is known to counteract authophagy, increasing evidence revealed a down-regulation of miR-29a in HCC patients which correlates with poor prognosis. Beside, evidences showed that miR-29a serves as a negative regulator of autophagy in other cancers. In the current study, we aim to investigate the impact of miR-29a on the autophagy and apoptosis in HCC cells using extracellular vesicles (EVs) as a natural delivery system given their potential in the miRNA delivery both in vitro and in vivo. Method: Human Wharton's Jelly mesenchymal stromal cell-derived extracellular vesicles were lately isolated through 20,000 or 110,000 × g centrifugation (EV20K or EV110K, respectively), characterized by western blot (WB), scanning electron microscopy (SEM), and dynamic light scattering (DLS). miR-29a was subsequently loaded into these EVs and its loading efficiency was evaluated via RT-qPCR. Comprehensive in vitro and in vivo assessments were then performed on Huh-7 and HepG2 cell lines. Results: EV20K-miR-29a treatment significantly induces cell apoptosis and reduces both cell proliferation and colony formation in Huh-7 and HepG2 cell lines. In addition, LC3-II/LC3-I ratio was increased while the expression of key autophagy regulators TFEB and ATG9A were downregulated by this treatment. These findings suggest an effective blockade of autophagy by EV20K-miR-29a leading to apoptosis in the HCC cell lines through concomitant targeting of critical mediators within each pathway. © 2024 Elsevier B.V.
dc.description.sponsorshipThis work was supported by Lutus (No. 400000079), and Bahar Tashkhis Teb Co. (BTT, 00/B/71). M.C is supported by grant RYC2021-031003I funded by MICIU/AEI/ https://doi.org/10.13039/501100011033 and, by European Union NextGenerationEU/PRTR. Funding text 2 The authors would like to express sincere gratitude to Dr. Paria Pooyan, Dr. Shokofeh Torabi, and other supporting colleagues at Royan Institute core facilities in the stem cell department. Animal Studies: All animal experiments were performed under the Guide for the Care and Use of Laboratory Animals (National Institutes of Health Publication No. 80\u201323, revised 1996) and approved by the Research and Ethics Committee of Royan Institute (Approval No. IR.ACECR.ROYAN.REC.1400.107). Approval of the research protocol by an Institutional Reviewer Board: All animal experiments were approved by the Research and Ethics Committee of Royan Institute (Approval No. IR.ACECR.ROYAN.REC.1400.107).
dc.identifier.citationSeydi, H., Nouri, K., Shokouhian, B., Piryaei, A., Hassan, M., Cordani, M., ... & Vosough, M. (2024). MiR-29a-laden extracellular vesicles efficiently induced apoptosis through autophagy blockage in HCC cells. European Journal of Pharmaceutics and Biopharmaceutics, 203, 114470.
dc.identifier.doi10.1016/j.ejpb.2024.114470
dc.identifier.issn09396411
dc.identifier.scopus2-s2.0-85202564068
dc.identifier.scopusqualityQ1
dc.identifier.urihttp://dx.doi.org/10.1016/j.ejpb.2024.114470
dc.identifier.urihttps://hdl.handle.net/20.500.12713/6919
dc.identifier.volume203
dc.identifier.wosWOS:001304630600001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakScopus
dc.indekslendigikaynakWeb of Science
dc.institutionauthorZarrabi, Ali
dc.institutionauthoridAli Zarrabi / 0000-0003-0391-1769
dc.language.isoen
dc.publisherElsevier B.V.
dc.relation.ispartofEuropean Journal of Pharmaceutics and Biopharmaceutics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectApoptosis
dc.subjectAutophagy
dc.subjectExtracellular Vesicles
dc.subjectHepatocellular Carcinoma
dc.subjectMiR-29a
dc.subjectTherapeutic Targeting
dc.titleMiR-29a-laden extracellular vesicles efficiently induced apoptosis through autophagy blockage in HCC cells
dc.typeArticle

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