MiR-124 inhibits the growth of glioblastoma through the downregulation of SOS1

Abstract

Glioblastoma multiforme (GBM) is a lethal brain tumor in adults. Despite advances in treatments, such as surgery, radiotherapy and chemotherapy, high‑grade glioma remains fatal. The molecular and cellular mechanisms for GBM are not entirely clear and further studies are required to elucidate these. MicroRNAs (miRNAs) are small, non‑coding, endogenous RNAs that are involved in cell differentiation and proliferation, and have been suggested to play a role in a variety of types of cancer. In this study, we investigated the role of miR-124 in the inhibition of proliferation of GBM cells. The downregulation of miR-124 in human GBM tumor cell lines was detected using quantitative RT-PCR. To assess the function of miR-124, we constructed stable cell lines, U87-124 and U373-124, which overexpressed miR-124 using lentiviral vectors. Overexpression of miR-124 inhibited the proliferation of GBM cancer cells in vitro. Using integrated bioinformatics analysis, SOS1 was found to be a direct target for miR-124, which is frequently upregulated in gliomas. Dual‑luciferase reporter assays confirmed that the SOS1 mRNA 3'‑untranslated regions (UTR) was directly targeted by miR-124 and that the mutated 3'UTR was not affected. This was revealed to be mechanistically associated with the induction of SOS/Ras/Raf/ERK and the suppression of ERK activity, which was achieved by silencing SOS1. This study therefore indicates an important role for miR-124 in the regulation of growth in the molecular etiology of GBM, and offers a potential strategy for the use of miR-124 in cancer treatment.