MiR‑296‑3p promotes the proliferation of glioblastoma cells by targeting ICAT.

Abstract

MicroRNAs (miRNA/miRs) serve an important function in the regulation of gene expression, and have been indicated to mediate a number of cellular biological processes, including cell proliferation, the cell cycle, cell apoptosis and cell differentiation. The altered expression of miRNAs has been revealed to result in a variety of human diseases, including glioblastoma multiforme (GBM). The present study indicated an increase in miR-296-3p in glioma tumor types compared with normal brain, particularly in the samples from patients with high grade GBM. Antagonizing miR-296-3p was demonstrated to induce cell growth arrest and cell cycle redistribution in U251 cells. The miR-296-3p antagonist altered the expression of a number of key genes that are involved in cell cycle control, including cyclin D1 and p21. Additionally, the decrease of miR-296-3p increased inhibitor of β-catenin and T cell factor (ICAT) expression, and increased miR-296-3p-inhibited ICAT expression in U251 cells. Bioinformatics analysis indicated that ICAT is a target gene of miR-296-3p, which was further validated using a dual-luciferase reporter assay. Through the regulation of ICAT, the miR-296-3p antagonist decreased β-catenin protein expression and increased the expression of its target genes. Silencing ICAT was indicated to reverse the miR-296-3p downregulation-induced inactivation of Wnt signaling and cell growth arrest in glioma cells. The present study also indicated a negative correlation between ICAT mRNA levels and miR-296-3p levels in glioma tumor types. In conclusion, the present study identified an oncogenic function of miR-296-3p in glioblastoma via the direct regulation of ICAT.