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.