miR­296­3p promotes the proliferation of glioblastoma cells by targeting ICAT.

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 miR­296­3p in glioma tumor types compared with normal brain, particularly in the samples from patients with high grade GBM. Antagonizing miR­296­3p was demonstrated to induce cell growth arrest and cell cycle redistribution in U251 cells. The miR­296­3p 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 miR­296­3p increased inhibitor of ß­catenin and T cell factor (ICAT) expression, and increased miR­296­3p­inhibited ICAT expression in U251 cells. Bioinformatics analysis indicated that ICAT is a target gene of miR­296­3p, which was further validated using a dual­luciferase reporter assay. Through the regulation of ICAT, the miR­296­3p antagonist decreased ß­catenin protein expression and increased the expression of its target genes. Silencing ICAT was indicated to reverse the miR­296­3p downregulation­induced inactivation of Wnt signaling and cell growth arrest in glioma cells. The present study also indicated a negative correlation between ICAT mRNA levels and miR­296­3p levels in glioma tumor types. In conclusion, the present study identified an oncogenic function of miR­296­3p in glioblastoma via the direct regulation of ICAT.