hsa-miR-181a-5p inhibits glioblastoma development via the MAPK pathway: in-silico and in-vitro study  

作　　者：MAHDI ABDOLI SHADBAD BEHZAD BARADARAN 

机构地区：[1]Student Research Committee,Tabriz University of Medical Sciences,Tabriz,Iran [2]Immunology Research Center,Tabriz University of Medical Sciences,Tabriz,Iran

出　　处：《Oncology Research》2024年第12期1949-1958,共10页肿瘤学研究（英文）

摘　　要：Background:Glioblastoma remains a highly invasive primary brain malignancy with an undesirable prognosis.Growing evidence has shed light on the importance of microRNAs(miRs),as small non-coding RNAs,in tumor development and progression.The present study leverages the in-silico and in-vitro techniques to investigate the significance of hsa-miR-181a-5p and the underlying hsa-miR-181a-5p-meidated signaling pathway in glioblastoma development.Methods:Bioinformatic studies were performed on GSE158284,GSE108474(REMBRANDT study),TCGA-GTEx,CCLE,GeneMANIA,Reactome,WikiPathways,KEGG,miRDB,and microT-CDS to identify the significance of hsa-miR-181a-5p and its underlying target.Afterward,the U373 cell line was selected and transfected with hsa-miR-181a-5p mimics,and the cell viability,clonogenicity,migration,mRNA expression,apoptosis,and cell cycle were studied using the MTT assay,colony formation test,migration assay,qRT-PCR,andflow cytometry respectively.Results:hsa-miR-181a-5p expression is decreased in glioblastoma samples.The in-silico results have shown that hsa-miR-181a-5p could regulate the MAPK pathway by targeting AKT3.The experimental assays have shown that hsa-miR-181a-5p decreases the migration of glioblastoma cells,arrests the cell cycle,and increases the apoptosis rate.Besides downregulating MMP9 and upregulating BAX,hsa-miR-181a-5p downregulates MET,MAP2K1,MAPK1,MAPK3,and AKT3 expression in U373 cells.The in-vitro results were consistent with in-silico results regarding the regulatory effect of hsa-miR-181a-5p on the MAPK pathway,leading to tumor suppression in glioblastoma.Conclusions:hsa-miR-181a-5p inhibits glioblastoma development partially by regulating the signaling factors of the MAPK pathway.

关 键 词：GLIOBLASTOMA hsa-miR-181a-5p MAPK MICRORNAS 

分 类 号：R739.4[医药卫生—肿瘤]