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

IF 4.7 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research Pub Date : 2024-08-03 DOI:10.1016/j.arcmed.2024.103061

Abouzar Babaei , Amin Torabi Yazdi , Reza Ranji , Ensiyeh Bahadoran , Shiva Taheri , Farhad Nikkhahi , Saied Ghorbani , Ardeshir Abbasi

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引用次数: 0

Abstract

Background and aim

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.

Method

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.

Results

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.

Conclusion

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.

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脂肪组织来源干细胞的外泌体 miRNA-4731-5p 对人类胶质母细胞瘤细胞的治疗作用

背景和目的：有几种微RNA（miRNA）在胶质母细胞瘤（GBM）中有不同程度的表达，并可作为肿瘤抑制因子。本研究旨在阐明来自脂肪组织间充质干细胞（AD-MSCs）的外泌体microRNA-4731-5p（miR-4731-5p）在人类GBM细胞系活性中的功能：方法：首先，利用生物信息数据集确定了与GBM相关的miRNA及其表达，以及miR-4731-5p的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-MSCs，并分离和鉴定外泌体。接下来，对转染过程进行了确认，并抑制了过表达的外泌体 miRNA-4731-5p 对癌细胞的 50% 抑制浓度（IC50）。通过流式细胞术、DAPI 染色、细胞周期、实时 PCR 和伤口愈合试验，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：结果：miRNA-4731-5p转染的外泌体浓度为50纳克/毫升，是抗癌的安全剂量。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-kB）信号通路，对GBM细胞株的细胞周期和迁移产生抑制作用，并诱导细胞凋亡：本研究揭示了外泌体miRNA-4731-5p的表达在治疗GBM细胞系方面具有良好的抗肿瘤特性，可能成为这类脑肿瘤的基本治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Archives of Medical Research 医学-医学：研究与实验

CiteScore

12.50

自引率

0.00%

发文量

审稿时长

28 days

期刊介绍： Archives of Medical Research serves as a platform for publishing original peer-reviewed medical research, aiming to bridge gaps created by medical specialization. The journal covers three main categories - biomedical, clinical, and epidemiological contributions, along with review articles and preliminary communications. With an international scope, it presents the study of diseases from diverse perspectives, offering the medical community original investigations ranging from molecular biology to clinical epidemiology in a single publication.