早发性卵巢功能不全的lncRNA-miRNA-mRNA网络的构建和生物信息学分析

Construction and bioinformatics analysis of lncRNA-miRNA-mRNA network in premature ovarian insufficiency

目的:探讨lncRNA相关内源竞争RNA(ceRNA)网络在早发性卵巢功能不全中的作用机制。方法:从Gene Expression Omnibus(GEO)数据库中筛选出两个早发性卵巢功能不全患者的数据集,使用R语言“limma”包筛选出差异表达的lncRNA、miRNA和mRNA。使用Starbase数据库预测与差异lncRNA相互作用的miRNAs,使用TargetScan和miRDB数据库预测与差异miRNAs相互作用的mRNAs,预测的mRNAs与差异mRNAs取交集。根据RNA之间的相互作用关系,建立早发性卵巢功能不全的lncRNA-miRNA-mRNA ceRNA调控网络。使用Metascape在线工具对ceRNA调控网络中的mRNA进行GO和KEGG功能分析,通过String数据库建立蛋白质相互作用(PPI)网络,利用Cytohubba插件识别PPI网络中的hub基因并构建lncRNAmiRNA-hub基因网络。结果:从早发性卵巢功能不全患者与正常对照组中筛选了116个差异lncRNAs,22个差异miRNAs和282个差异mRNAs。通过116个差异lncRNAs,利用数据库预测到了13个差异lncRNAs,7个差异miRNAs和54个差异mRNAs的相互作用,构建了早发性卵巢功能不全的lncRNA-miRNA-mRNA ceRNA调控网络。GO和KEGG富集分析结果显示,调控网络中的mRNA参与早发性卵巢功能不全的生物学过程,包括凋亡信号通路、mRNA的代谢过程和cAMP信号通路。通过PPI网络筛选了8个hub基因(EIF4ENIF1、SENP1、RBM5、DYNLL2、AGO2、SRSF1、CAPZB、SRSF10),构建了一个lncRNA-miRNA-hub基因网络。结论:12个lncRNA通过参与SRSF1等hub基因的表达,调控影响早发性卵巢功能不全的发生、发展。

Objective:To explore the mechanism of lncRNA related endogenous competitive RNA(ceRNA)regulatory network in premature ovarian insufficiency.Methods:Two data sets about premature ovarian insufficiency patients and healthy controls were screened from the Gene Expression Omnibus(GEO)database.Differentially expressed lncRNAs,miRNAs and mRNAs were identified by"limma"package of R software.The miRNAs interacting with differentially expressed lncRNAs were predicted by the Starbase database,TargetScan and miRDB databases were used to predict mRNAs that interact with the differentially expressed miRNAs,and the predicted mRNAs were intersected with differentially expressed mRNAs.Based on the interactions between RNAs,a lncRNA-miRNAmRNA ceRNA regulatory network for premature ovarian insufficiency was established.GO and KEGG functional analysis of mRNA in ceRNA network was performed by"Metascape"online analysis tools,and protein-protein interaction(PPI)network was established by String database.The Cytohubba plugin of Cytoscape was used to identify hub genes in the PPI network,and a lncRNA-miRNA-hub gene network was constructed.Results:116 differentially expressed lncRNAs,22 differentially expressed miRNAs and 282 differentially expressed mRNAs were identified between premature ovarian insufficiency patients and normal controls.Based on the 116 lncRNAs,the interaction of 13 differentially expressed lncRNAs,7 differentially expressed miRNAs and 54 differentially expressed mRNAs were pre-dicted by the database,the lncRNA-miRNA-mRNA ceRNA network of premature ovarian insufficiency was constructed.The results of GO and KEGG analysis showed that the mRNAs in the ceRNA network were involved in premature ovarian insufficiency related biologi-cal processes,including apoptosis signaling pathway,regulation of mRNA metabolic process,cAMP signaling pathway.We identified 8 hub genes from the PPI network(EIF4ENIF1,SENP1,RBM5,DYNLL2,AGO2,SRSF1,CAPZB,SRSF10)and constructed a lncRNAmiRNA-hub gene network.Conclusion:Twelve lncRNAs influence the occurrence and development of premature ovarian insufficiency by participating in expression of hub gene SRSF1 and so on.