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Hsa-Mir-3529-5P Through F2rl3 Regulation As an Enhancer of Sensitivity to Cisplatin Publisher



Ns Moghaddam Nasibeh SARGAZI ; B Mohammadfakhim BAHARAK ; M Sharifi MOHAMMAD ; A Rajabian ATEFEH ; M Hariri MARYAM ; M Khansari MAHMOUD ; M Saeed Soleimani Meigoli MOHAMMAD ; R Morovatshoar REZA ; S Hosseini SAHAR ; Nj Namini Niloufar JAFARI
Authors

Source: Indian Journal of Clinical Biochemistry Published:2024


Abstract

The emergence of drug resistance in gastric cancer presents a critical challenge in oncological treatments, often leading to therapy failure and reduced patient survival. MicroRNAs (miRNAs) have been implicated in modulating drug resistance through various mechanisms, including altering the expression of genes involved in drug metabolism, DNA repair, and apoptosis. This study aimed to elucidate the role of miR-3529-5p in cisplatin resistance in gastric cancer by investigating its interaction with the gene F2RL3, which was identified as significantly overexpressed in cisplatin-resistant gastric cancer cells. Using RNA sequencing data and bioinformatics tools, differentially expressed genes (DEGs) were identified between cisplatin-resistant and sensitive cell lines, with F2RL3 emerging as a key gene overexpressed in resistant cells. The overexpression of miR-3529-5p using the pbud-egfb vector in AGS cells was conducted, followed by MTT assays to assess cell viability and resistance to cisplatin. qPCR was used to compare the expression of apoptosis-related genes between AGS/cis cells and AGS/miR-3529-5p/cis cells, while flow cytometry was employed to examine apoptosis levels. The results confirmed that increased miR-3529-5p expression leads to reduced F2RL3 levels, enhancing cell sensitivity to cisplatin. Cell viability assays showed a decrease in the IC50 of cisplatin in miR-3529-5p-overexpressing cells, indicating heightened drug sensitivity. Furthermore, gene expression analysis and apoptosis assays demonstrated that miR-3529-5p modulates apoptosis-related genes, promoting apoptosis in the presence of cisplatin. In conclusion, miR-3529-5p plays a significant role in reversing cisplatin resistance in gastric cancer by targeting F2RL3, suggesting its potential as a therapeutic target to enhance cisplatin efficacy in gastric cancer treatment. © 2024 Elsevier B.V., All rights reserved.
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