Hsa-miR-650通过靶向RAC1抑制NF2阴性脑膜瘤的生长

Hsa-miR-650 Inhibits NF2-negative Meningioma Growth by Targeting RAC1

目的本文旨在确定NF2表达阴性脑膜瘤中潜在的miRNA-mRNA轴,研究它们的靶向关系,并确定它们的生物学功能。方法从基因表达数据库(GEO)下载包含与NF2阴性脑膜瘤相关数据的GSE17792数据集。使用R软件中的limma包确定差异表达的mi RNA(De MiRNAs)。应用miRWalk 2.0数据库获取De MiRNAs的靶基因。利用相互作用基因检索工具(STRING)数据库构建蛋白质相互作用(PPI)网络,并通过Cytoscape软件确定核心基因。对筛选出的miRNA进一步验证其表达和生物学作用。结果在NF2阴性脑膜瘤肿瘤样本与蛛网膜组织对照组比较中发现了86个差异mi RNA,其中包括52个上调的mi RNAs和34个下调的miRNAs。在这些差异miRNA中鉴定出与274个靶基因相关的14个mi RNAs,并基于这些数据构建miRNA-靶基因网络。通过cyto Hubba分析显示,在PPI网络中有两个mi RNAs(hsa-miR-650和hsa-miR-623)位于前20个关键核心基因之中。进一步的定量逆转录PCR(q RT-PCR)实验证实,相对于正常脑组织,hsa-miR-650在NF2阴性脑膜瘤中的表达显著增高。下调hsa-miR-650抑制了NF2阴性脑膜瘤细胞的增殖并诱导细胞凋亡。最后,确定RAC1是hsa-miR-650的靶基因。结论Hsa-miR-650作为肿瘤促进剂,可能作为治疗NF2阴性脑膜瘤患者的治疗靶点。

Objective This study aimed to identify a potential miRNA-mRNA axis in neurofibromatosis type 2(NF2)-negative meningiomas,investigate their target relationships,and determine their biological functions.Methods The GSE17792 dataset,which contains data related to NF2-negative meningiomas,was downloaded from the Gene Expression Omnibus(GEO)database.The limma package of R software was used to determine the differentially expressed miRNAs(DeMiRNAs).The miRWalk 2.0 database was applied to obtain the target genes of DeMiRNAs.The Search Tool for the Retrieval of Interacting Genes(STRING)database was utilized to build protein-protein interaction(PPI)networks,and hub genes were identified via Cytoscape software.The expression and biological roles of the screened miRNAs were further validated.Results Altogether,86 DeMiRNAs,consisting of 52 upregulated and 34 downregulated miRNAs,were found in NF2-negative meningioma tumor samples compared with arachnoid tissue controls.Fourteen miRNAs associated with 274 target genes were identified among these DeMiRNAs,and miRNA-target gene networks were constructed based on these data.Analysis with cytoHubba showed that two miRNAs(hsa-miR-650 and hsa-miR-623)were among the top 20 key hub genes in the PPI network.Further qRT-PCR experimental verification suggested that the expression of hsa-miR-650 was significantly higher in NF2-negative meningiomas than in normal brain tissues.Downregulation of hsa-miR-650 inhibited the proliferation and induced the apoptosis of NF2-negative meningioma cells.Finally,RAC1 was identified as a target of hsa-miR-650.Conclusion Hsa-miR-650 acts as a tumor promoter and might function as a therapeutic target for patients with NF2-negative meningiomas.