Effect And Mechanism Of MiRNA-375 On Glioma Proliferation And Apoptosis

Background Glioma is the most common primary tumor in the central nervous system.According to the American Brain Cancer Society data,gliomas account for 24.7% of all primary brain tumors,accounting for 74.6% of all malignancies.Although the current treatment includes surgery followed by radiotherapy and chemiotherapy,such as temozolomide,the tumor reappears with an average survival of about 15 months.The use of a low-intensity,mid-frequency alternating electric field combined with standard chemoradiotherapy to treat patients increases the overall survival time to 19.4 months in the newly diagnosed glioblastoma patients.However,surviving patients with gliomas often suffer from a long list of damaging long-term side effects.Therefore,a better understanding of the molecular mechanisms of disease remains crucial to developing new therapeutic strategies.Mi RNA-375 plays an important regulatory role in tumorigenesis and progression,and plays a regulatory role in the proliferation,invasion and apoptosis of cancer.Methods: Thirty tumor samples of brain gliomas and 30 brain samples of large area cerebral infarction(paraffin-embedded sections)were collected respectively.The expression of miRNA-375 and connective tissue growth factor(CTGF)protein were detected by in situ hybridization(ISH)and immunohistochemistry(IHC)respectively.In glioma cell lines,U87 cells were divided into 3 groups: NC group(cells were treated by normal methods);BL group(cells transfected with empty vector)and miRNA group(U87 cells transfected with miRNA-375).MTT assay 3 groups of cells proliferation.Flow cytometry was used to detect the apoptosis rate and cell cycle of U87 cells in each group.The expression of related proteins(CTGF,EGFR,AKT,Erk and P21)was detected by WB method.Results:1.The expression of miRNA-375 in glioma tissue was significantly lower than that in non-tumor tissue by ISH detection(P <0.05).2.The results of IHC showed that the expression of CTGF in glioma tissue was higher than that in non-tumor tissue(P <0.05).3.Cell proliferation experiments suggest that miRNA group cell proliferation rate was significantly lower than the NC group and BL group(P <0.05).4.Compared with NC group and BL group,the apoptosis rate of miRNA group and the proportion of cells in G1 phase were significantly different(P <0.05).5.According to the WB experiments,the expression of CTGF,EGFR,AKT,Erk and P21 in miRNA group was significantly different from that in NC group(P <0.05).Conclusions:1.miRNA-375 overexpression can inhibit the proliferation of glioma.2.miRNA-375 overexpression can promote the apoptosis of glioma.3.miRNA-375 inhibits glioma cell development through the CTGF-EGFR pathway.