MiR-373/miR-520s-CD44 Axis Significantly Inhibits the Growth and Invasion of Human Glioblastoma Cells

Abstract

The expression and regulation of microRNAs (miRNAs) play an important role in glioblastoma (GBM) tumorigenesis, progression and prognosis. Little is known about the role of the miRNA regulatory network of GBM risk-related genes in GBM growth and invasiveness. The UALCAN and Oncomine gene expression dataset were used to explore gene expression profiles in human GBM. The Kaplan-Meier method was performed to evaluate the prognostic values of the GBM-related genes. Multiple bioinformatics databases were analysed to predict the GBM-related genes targeted by miRNAs. A luciferase reporter assay and other molecular cell function experiments were conducted to reveal the mechanisms of interaction between the identified miRNAs and their targets. The CD44 expression is significantly higher in GBM tissues than that in normal tissues, and negatively correlated with survival duration in GBM patients. In normal physiological conditions, CD44 expression is lower in various parts of the central nervous system than in other organ systems. The mRNA encoding CD44 is a direct target of miR-373 and miR-520s, and this finding was verified by molecular biology experiments. We further found that miR-373 and miR-520s expression was negatively associated with CD44 expression in GBM specimens, and that the miR-373 or miR-520s-CD44 interaction network significantly affected the growth and invasiveness of GBM cells. The miR-373 and miR-520s exert their functions by suppressing CD44 expression in GBM cells, and their expression, together with that of CD44, could thus serve as a valuable biomarker of GBM prognosis.