RT Journal Article
T1 MiR-29a-laden extracellular vesicles efficiently induced apoptosis through autophagy blockage in HCC cells
A1 Seydi, Homeyra
A1 Nouri, Kosar
A1 Shokouhian, Bahare
A1 Piryaei, Abbas
A1 Hassan, Moustapha
A1 Cordani, Marco
A1 Zarrabi, Ali
A1 Shekari, Faezeh
A1 Vosough, Massoud
AB Background. 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.
PB Elsevier
SN 0939-6411
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.14352/112307
UL https://hdl.handle.net/20.500.14352/112307
LA eng
NO Seydi, H., Nouri, K., Shokouhian, B., Piryaei, A., Hassan, M., Cordani, M., Zarrabi, A., Shekari, F., & Vosough, M. (2024). MiR-29a-laden extracellular vesicles efficiently induced apoptosis through autophagy blockage in HCC cells. European Journal of Pharmaceutics and Biopharmaceutics, 203. https://doi.org/10.1016/J.EJPB.2024.114470
NO This 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.
NO Ministerio de Ciencia, Innovación y Universidades (MICIU)
NO European Commission
DS Docta Complutense
RD 14 dic 2025