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

in Archives of medical research by Abouzar Babaei, Amin Torabi Yazdi, Reza Ranji, Ensiyeh Bahadoran, Shiva Taheri, Farhad Nikkhahi, Saied Ghorbani, Ardeshir Abbasi

TLDR

  • The study found that a type of tiny particles called exosomes from a type of stem cells called mesenchymal stem cells (MSCs) can help fight against a type of brain tumor called glioblastoma (GBM). The study found that the exosomes from the MSCs can help stop the growth of the GBM cells and even make them die. The study also found that the safe dose for using the exosomes to fight against GBM is 50 ng/mL. The study suggests that the exosomes from the MSCs could be a new way to treat GBM and that more research is needed to make sure it is safe and effective.

Abstract

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.

Overview

  • The study aims to investigate 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. The study uses bioinformatic datasets to identify GBM-related miRNAs, their expression, and potential target genes and cytokines of miR-4731-5p. Purified AD-MSCs are transfected with a miRNA-4731-5p expression plasmid, and exosomes are isolated and characterized. The study verifies the probable anticancer action of exosomal miRNA-4731-5p on U-87 and U-251 GBM cell lines by flow cytometry, DAPI staining, cell cycle, real-time PCR, and wound healing assays. The study concludes 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.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The study identifies that exosomal miRNA-4731-5p exerts an inhibitory effect on the cell cycle and migration and induces apoptosis in GBM cell lines by regulating the PI3K-AKT and NF-kB signaling pathways. The study also identifies that the concentration of 50 ng/mL of miRNA-4731-5p-transfected exosomes is the safe dose for anticancer settings.

Implications and Future Directions

  • The study's findings suggest that 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. The study identifies that the concentration of 50 ng/mL of miRNA-4731-5p-transfected exosomes is the safe dose for anticancer settings. The study also identifies 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. The study suggests that future research should focus on the development of a safe and effective delivery system for exosomal miRNA-4731-5p to enhance its therapeutic potential.
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