研究动态
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脂肪组织干细胞外泌体 miRNA-4731-5p 对人胶质母细胞瘤细胞的治疗作用。

Therapeutic Effects of Exosomal miRNA-4731-5p from Adipose Tissue-Derived Stem Cells on Human Glioblastoma Cells.

发表日期:2024 Aug 03
作者: Abouzar Babaei, Amin Torabi Yazdi, Reza Ranji, Ensiyeh Bahadoran, Shiva Taheri, Farhad Nikkhahi, Saied Ghorbani, Ardeshir Abbasi
来源: ARCHIVES OF MEDICAL RESEARCH

摘要:

几种 microRNA (miRNA) 存在差异表达,并在胶质母细胞瘤 (GBM) 中充当肿瘤抑制因子。本研究旨在阐明脂肪组织源性间充质干细胞(AD-MSCs)外泌体微小RNA-4731-5p(miR-4731-5p)在人GBM细胞系活性中的功能。使用生物信息学数据集鉴定了 miR-4731-5p 的表达、潜在靶基因和细胞因子。随后,用 miRNA-4731-5p 表达质粒转染纯化的 AD-MSC,并分离和表征外泌体。接下来,确认了转染过程,并且过表达的外泌体miRNA-4731-5p对癌细胞的抑制浓度为50%(IC50)。通过流式细胞术、DAPI 染色、细胞周期、实时 PCR 和伤口愈合测定验证了外泌体 miRNA-4731-5p 对 U-87 和 U-251 GBM 细胞系的可能抗癌作用。浓度为 50 ng/ mL 的 miRNA-4731-5p 转染的外泌体是抗癌环境的安全剂量。结果表明,外泌体miR-4731-5p通过调节磷酸肌醇3激酶-AKT(PI3K-AKT)和核因子-kB(NF)对GBM细胞系的细胞周期和迁移产生抑制作用并诱导细胞凋亡。 -kB) 信号通路。这项研究表明,外泌体 miRNA-4731-5p 的表达对于 GBM 细胞系的治疗具有良好的抗肿瘤特性,可能是此类脑肿瘤的基本治疗选择。版权所有 © 2024。出版者爱思唯尔公司
Several microRNAs (miRNAs) are differentially expressed and serve as tumor suppressors in glioblastoma (GBM). The present study aimed to elucidate the function of exosomal microRNA-4731-5p (miR-4731-5p) from adipose tissue-derived mesenchymal stem cells (AD-MSCs) in the activity of human GBM cell lines.First, GBM-related miRNAs, their expression, and potential target genes and cytokines of miR-4731-5p were identified using bioinformatic datasets. Subsequently, purified AD-MSCs were transfected with a miRNA-4731-5p expression plasmid, and exosomes were isolated and characterized. Next, the transfection process was confirmed and the 50% inhibitory concentration (IC50) of the overexpressed exosomal miRNA-4731-5p was inhibited for cancer cells. The probable anticancer action of exosomal miRNA-4731-5p on U-87 and U-251 GBM cell lines was verified by flow cytometry, DAPI staining, cell cycle, real-time PCR, and wound healing assays.A concentration of 50 ng/mL of miRNA-4731-5p-transfected exosomes was the safe dose for anticancer settings. The results showed that the exosomal miR-4731-5p exerted an inhibitory effect on the cell cycle and migration and induced apoptosis in GBM cell lines by regulating the phosphoinositide-3-kinase-AKT (PI3K-AKT) and nuclear factor-kB (NF-kB) signaling pathways.This study reveals that the expression of exosomal miRNA-4731-5p has favorable antitumor properties for the treatment of GBM cell lines and may be a fundamental therapeutic option for this type of brain tumor.Copyright © 2024. Published by Elsevier Inc.