MiRNA-1231 Inhibits Glioma Cell Growth And Arrests Cell Cycle By Targeting EGFR

Research background and purpose:Glioma is the most common primary central nervous system tumor in adults,in particular,Glioblastoma multiforme(GBM)has the highest degree of malignancy,with the highest mortality rate.Despite the current standard treatment for glioma includes surgery,radiotherapy,chemotherapy and molecular targeted therapy,the prognosis for patients with malignant gliomas is still poor.Therefore,it is particularly important to explore new and effective treatment for glioma.MicroRNAs(miRNAs)are a group of short non-coding single-stranded endogenous RNA molecules,about 20 nucleotides in length,that regulate their target genes by inhibiting the translation process and degrading mRNA.Data show that about 30% of genes in humans are predicted to be regulated by miRNAs.Recently,some miRNAs have been proved to inhibit the intracellular signaling pathway by regulating its target genes,which is involved in the regulation of tumor proliferation,differentiation,apoptosis and immunomodulation.Epidermal growth factor receptor(EGFR)is an important member of the ErbB receptor family,which are widely distributed on the surface of mammalian epithelial cells.EGFR has been shown to induce the activation of multiple kinase signaling pathways in cells after activation,among which phosphatidylinositol kinase-3-protein kinase(PI3K-AKT)signal transduction pathway is common.This signaling pathway activates gene transcription in turn and activates pathways that control cell proliferation,differentiation,and survival.Previous studies have shown abnormal expression of EGFR in many solid tumors of human,such as glioma,pancreatic cancer,breast infiltrating ductal carcinoma,renal cancer,and colorectal / rectal cancer.In our study,we found that the expression level of miRNA-1231 in glioma cells and specimens was significantly lower than that in normal human astrocytes and normal brain tissues.The results were similar by CGGA database analysis,and the level were negatively correlated with the World Health Organization(WHO)classification,the higher the glioma grade,the lower the miRNA-1231 expression.After overexpression of microRNA-1231,the proliferative ability of glioma cells decreased significantly,and more cells arrested in the G0/G1 phase of the cell cycle,while the cells after knocking down miRNA-1231 showed the opposite results.In order to further explore the mechanism of the effect of miRNA-1231 on glioma cells,it was found that miRNA-1231 affects the activity of signal pathway PI3K/AKT by acting on its downstream target gene EGFR,and the playing the role of cell proliferation inhibition and cell cycle arrest.Subsequently,the subcutaneous experiments in nude mice have also demonstrated this.Our results suggest that miRNA-1231 may play an important role of glioma suppressor by targeting EGFR to regulate PI3K/AKT,which provides a new perspective on the mechanism of glioma proliferation and cycle.And may become a new direction of molecular targeted therapy for glioma.