TFE3对胆汁淤积分子调控作用的整合生物信息学分析

Unraveling the molecular regulation mechanism of TFE3 on cholestasis through integrated bioinformatics analysis

拟使用生物信息学方法探索TFE3对胆汁淤积疾病的防御调控分子机制,为以TFE3为新靶点,开发防治胆汁淤积性疾病的药物提供理论依据.首先对胆道闭锁GEO数据库(GSE46960)进行加权基因共表达网络(WGCNA)分析,筛选出与疾病呈负相关的模块.该模块中的基因再与胆汁淤积GEO数据库(GSE152494、GSE169072)差异表达基因以及TFE3下游靶基因共同取交集,获得TFE3可能调节的对于胆汁淤积性疾病具有抑制作用的候选基因.最后利用JASPAR数据库分析TFE3与候选基因启动子CLEAR(coordinated lysosomal expression and regulation)序列结合的可能性.通过WGCNA分析共获得7个与疾病显著相关的模块,其中,4个模块与疾病呈显著负相关.这4个模块里的基因经与胆汁淤积数据库差异表达基因、GTRD预测的TFE3靶基因共同取交集,获得14个受TFE3调控的候选靶基因.JASPAR数据库分析TFE3与C4BPB、C9、DHODH、HAO2、HMGCS1和SC5D启动子上具有结合位点.该研究首次从生物信息学角度全面解析了TFE3对胆汁淤积性疾病保护作用的调节机理,推测TFE3可能通过调节这6个靶基因对胆汁淤积疾病起到防御保护作用.

In this article,we will using bioinformatics methods to explore the defense regulatory molecular mechanism of TFE3 on cholestasis.It provided a theoretical basis for the development of drugs for the prevention and treatment of cholestatic liver diseases with TFE3 as a new target.In this study,using bioinformatics methods,the weighted gene co-expression network(WGCNA)analysis was performed on the GEO database of biliary atresia(GSE46960).This genes in modules that were negatilvely related with disease were then intersected with the differentially expressed genes in the cholestasis GEO database(GSE152494-GPL570,GSE169072)and the downstream target genes of TFE3.Candidate genes that have inhibitory effects on cholestatic disease possibly regulated by TFE3 were obtained.Then,JASPAR database was used to analyze the possibility of binding between TFE3 and CLEAR(coordinated lysosomal expression and regulation)sequence on the candidate gene promoter.A total of 7 modules that are significantly related to the disease were obtained through WGCNA analysis,of which 4 modules were negatively related to the disease.14 candidate target genes regulated by TFE3 were obtained by the intersection of the genes in these 4 modules with the differentially expressed genes in the cholestasis database and the TFE3 target genes predicted by GTRD.JASPAR database analyzed that TFE3 has binding sites on the promoters of C4BPB,C9,DHODH,HAO2,HMGCS1 and SC5D.This study for the first time comprehensively unraveling the molecular regulation mechanism of TFE3 on cholestasis through integrated bioinformatics analysis.TFE3 may play a defensive and protective role against cholestatic diseases by regulating these six target genes.