The Mechanism Of MiR-520b/MBD2 Pathway In Malignant Progression Of Glioma

Research background and objective:MicroRNAs play an important role in the progression of cancer and it has been reported that microRNA-520b(miR-520b)plays a key role in the progression of many types of tumors.For example,miR-520 b inhibits tumor epithelial mesenchymalization by targeting the DCUN1D1 gene in colon cancer.However,the role of miR-520 b in gliomas is still less studied.In our study,miR-520 b was found to inhibit the growth and development of glioma by targeting methyl-CpG binding domain 2(MBD2).MBD2 binds to the NuRD complex and silences the gene through the complex methylation promoter.Studies have confirmed that MBD2 can act as a trigger for breast cancer to promote the malignant progression of the tumor.In this study,the clinical data and experimental data in the online database were analyzed to study the effect of miR-520 b and MBD2 on the biological behavior of glioma and explore its mechanism of action.Methods: 1.The microarray expression data of miRNA and mRNA in human glioma and normal brain tissue were downloaded from the Chinese Glioma Genome Atlas Database(CGGA).2.MiRNA fluorescence quantitative PCR using SYBR Green PCR reaction system and TaqMan reaction system.3.Logarithmic growth phase U87 and U251 cells were used to detect changes in biological behaviors such as glioma cell growth,invasion,and chemotherapeutic drug sensitivity through glucose uptake assay,Transwell assay,and angiogenesis assay.4.Bioinformatics predictions,luciferase reporter assays,RT-PCR,RNA pull down assays,and Western blot experiments validated the miR-520b’s targeted regulation of MBD2 and validated miR-520b/MBD2 signaling pathways.Results: 1.Compared with normal brain tissue,the expression of miR-520 b is down-regulated in glioma tissue.2.In vitro studies have shown that upregulation of miR-520 b expression can inhibit glucose uptake,invasion,angiogenesis and chemotherapeutic drug sensitivity in glioma cells.3.Bioinformatics,luciferase reporter assays,and Western Bolt experiments showed that miR-520 b binds directly to the 3‘-UTR region of MBD2 and regulates its expression.4.Further studies have shown that elevated MBD2 can partially reverse the down-regulation of MBD2 caused by up-regulation of miR-520 b and its anti-cancer effect.Conclusion:MiR-520 b directly targets and regulates the downstream gene MBD2,and clarifies the important role of miR-520b/MBD2 signaling pathway in vivo,and thus influences the progression of glioma.The discovery of this pathway provides a new idea for the study of glioma.