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

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.