基于lncRNA相关ceRNA网络预测冠心病血瘀证分子调控轴

Prediction on Molecular Regulation Axis of Coronary Heart Disease with Blood Stasis Syndrome Based on lncRNA-related ceRNA Network

目的通过长链非编码RNA(lncRNA)相关竞争性内源RNA(ceRNA)网络构建及分析,探讨冠心病血瘀证发生发展机制。方法通过HMDD、DisGeNET、OMIM、GeneCards、TTD、lncRNADisease数据库查找冠心病血瘀证相关基因,并通过starBase平台构建lncRNA相关ceRNA网络,采用MCODE、MCL、GLay方法识别功能模块,基于最小结构熵确定最优模块识别方法,筛选包含lncRNA、miRNA、mRNA的模块,通过文献预测模块中潜在的调控轴。结果ceRNA网络共有283个节点,由72个miRNA、182个mRNA、29个lncRNA和4990个调控关系组成,共划分为11个功能模块,发现UCA1-miR-1-G6PD调控轴,其中miR-1抑制G6PD表达导致冠状动脉疾病的发生,而UCA1能够解除miR-1的抑制从而恢复G6PD正常表达。结论UCA1-miR-1-G6PD分子调控轴与冠心病血瘀证相关;可通过ceRNA网络的模块化分析开展病证相关研究。

Objective To discuss the mechanism of occurrence and development of blood stasis syndrome in coronary heart disease through the construction and analysis of lncRNA-related ceRNA network.Methods Related genes of the disease-coronary artery disease and the phenotypes in blood stasis syndrome were searched from HMDD,DisGeNET,OMIM,GeneCards,TTD,lncRNADisease databases,and lncRNA-related ceRNA network was constructed through starBase platform.The MCODE,MCL,GLay methods were used to identify functional modules and the optimal module identification based on minimal structural entropy was obtained.After that,the modules which contained lncRNA,miRNA,and mRNA were screened,and the potential regulatory axis was predicted through literature analysis.Results The ceRNA network had a total of 283 nodes,consisting of 72 miRNAs,182 mRNAs,29 lncRNAs and 4990 regulatory relationships.A total of 11 functional modules were obtained.The UCA1-miR-1-G6PD regulatory axis was found,among which hsa-miR-1 inhibited the expression of G6PD,leading to the cause of coronary artery disease,while UCA1 could relieve the inhibition of miR-1 and recover the normal expression of G6PD.Conclusion UCA1-miR-1-G6PD molecular regulatory axis is related to the pathogenesis of coronary heart disease with blood stasis syndrome,which can conduct disease-syndrome-related research through modular analysis of ceRNA network.