MiR-124 Inhibits The Growth Of Glioblastoma Through The Downregulation Of SOS1

Objective 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.Micro RNAs(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 m RNA3’_untrans-lated regions(UTR)was directly targeted by miR-124 and that the mutated3’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.Methods We application the virus turn to dye of lead expression miR-124 of the stable cell fasten U87-124 and U373-124 and repressed increasing in value of bodyoutside glioma quality cell and applied aliving creature information to integrate.analysis over the miR-124 of expression,the SOS1 are the target that the negatives miR-124 s regulate the glioma quality cell to order examine an analysis confirmation miR-124 the direct function is at the SOS1 m RNA 3’(UTR),but not the function is at the mutation type of 3’(UTR).Results the SOS1 m RNA 3’_untrans-lated regions(UTR)was directly targeted by miR-124 and that the mutated 3’UTR was not affected.miR-124 is downregulated in GBM cell lines and the stable overexpression of miR-124 inhibits cell growth.Conclusion our study demonstrates that downregulated miR-124 is responsible for the upregulation of SOS1 in GBM,and miR-124 has an important role in inhibiting cell growth by regulating the SOS1/Raf/ERK signaling pathway.Our find-ings bring new insights on the targeted delivery of miR-124 to GBM cells as a potential therapeutic treatment for GBM.