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

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.