{"title":"Therapeutic Effects of Exosomal miRNA-4731‐5p from Adipose Tissue-Derived Stem Cells on Human Glioblastoma Cells","authors":"Abouzar Babaei , Amin Torabi Yazdi , Reza Ranji , Ensiyeh Bahadoran , Shiva Taheri , Farhad Nikkhahi , Saied Ghorbani , Ardeshir Abbasi","doi":"10.1016/j.arcmed.2024.103061","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and aim</h3><p>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.</p></div><div><h3>Method</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"55 7","pages":"Article 103061"},"PeriodicalIF":4.7000,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Medical Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0188440924001139","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
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.
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.