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

Zhou,Jing; Du,Guobo; Fu,Hongmei

doi:10.3892/mmr.2020.11011

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

Authors:
- Jing Zhou
- Guobo Du
- Hongmei Fu
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Affiliations: Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
Published online on: March 3, 2020 https://doi.org/10.3892/mmr.2020.11011
Pages: 2151-2161
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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