| dc.description.abstract | Abstract
Introduction: Recent advancements in systemic chemotherapy and immunotherapy have significantly improved the survival rates of patients with advanced gastric cancer. However, treating patients in the later stages of this disease often results in poor outcomes, primarily due to metastasis and peritoneal involvement. Given recent studies highlighting the positive role of miR-365 in gastric cancer and its potential impact on the HIF1α pathway, this study aims to evaluate the effects of exosome-delivered miR-365, derived from the HUVEC cell line, on the HIF1α pathway in vitro, as well as to investigate the levels of apoptosis.
Materials and Methods: First, the HUVEC cell line (provided by the Iranian Genetic and Biological Resources Center), was cultured to isolate exosomes from its culture medium. Next, the effects of exosomes alone and miR-365 loaded into exosomes on the expression levels of HIF1α, mTOR, IL-6, and VEGFA proteins were examined. Additionally, cell apoptosis was investigated in the MKN-45 cell line (provided by the Iranian Genetic and Biological Resources Center).
Results: Treatment of MKN-45 cells with miR-365 loaded in exosomes resulted in a 70% reduction in HIF1α protein expression compared to the negative control. The level of IL-6 in MKN-45 cells treated with miR-365 was significantly reduced by more than 15-fold compared to the negative control. Specifically, the IL-6 level in control cells, measured using the ELISA technique, was 74.3 pg/ml, while in cells treated with miR-365, it dropped to 4.9 pg/ml. Furthermore, miR-365 led to a significant decrease in the expression of the mTOR and VEGFA genes in MKN-45 cells. In the apoptosis test using annexin-propidium iodide, it was found that 22.3% of MKN-45 cells underwent apoptosis, 15.1% experienced delayed apoptosis, and 4.46% of the cells underwent necrosis.
Conclusion: miR-365 loaded in exosomes extracted from the HUVEC cell line can reduce the expression of HIF1α in the MKN-45 cell line by reducing the expression of IL-6 and mTOR. In addition, miR-365 can reduce the expression of VEGF (inhibition of angiogenesis), induce apoptosis, and stop EMT (counteraction to metastasis) in the MKN-45 cell line by reducing the expression of HIF1α. | en_US |
