酒精性股骨头坏死竞争性内源RNA网络及潜在生物标志物的综合分析

Comprehensive analysis of competing endogenous RNA network and potential biomarkers in alcohol-induced osteonecrosis of the femoral head

背景:酒精性股骨头坏死与饮酒具有高度的相关性,然而其具体发病机制尚不明确且存在一定的个体差异。目的:构建酒精性股骨头坏死的基因网络图谱,进一步探索酒精性股骨头坏死的潜在发病机制。方法:从广西中医药大学第一附属医院骨二科招募3例酒精性股骨头坏死患者和3名健康志愿者,通过对其外周血进行基因测序筛选具有差异表达的mRNA和lncRNA,通过预测lncRNA-miRNA和miRNA-mRNA的相互作用靶点,使用cytoscape软件构建竞争性内源RNA调控网络。结果与结论:①通过差异表达分析从酒精性股骨头坏死样本中鉴定出了差异lncRNA 127个、差异mRNA 921个,通过靶基因预测共预测出了205个miRNA及5184个mRNA靶点,最终构建了包含3个lncRNA(SNHG3、MUC19、LINC00476)、5个miRNA(hsa-miR-146b-5p、hsa-miR-139-5p、hsa-miR-126-3p、hsa-miR-193a-3p、hsa-miR-135a-5p)和11个mRNA(PEX5、ACTR3B、CHMP4B、CSMD1、MTRF1、ZNF3、HTR7、NR5A2、SYT14、CASK、ING5)的ceRNA网络,涉及干细胞分化、炎症反应、神经内分泌、基因多态性等多种生物学过程。②结果表明,通过构建竞争性内源网络筛选出了一系列酒精性股骨头坏死潜在的生物标志物,为进一步研究其分子机制及治疗靶点提供了新思路。

BACKGROUND:Alcohol-induced osteonecrosis of the femoral head is highly correlated with alcohol consumption.However,its specific pathogenesis is still unclear and there are certain individual differences.OBJECTIVE:To investigate the potential pathogenesis of alcohol-induced osteonecrosis of the femoral head by constructing a gene network map of alcoholinduced osteonecrosis of the femoral head.METHODS:Three patients with alcohol-induced osteonecrosis of the femoral head and three healthy volunteers were recruited from the Second Department of Orthopedics in the First Affiliated Hospital of Guangxi University of Chinese Medicine.Differentially expressed mRNA and lncRNA were screened out through gene sequencing of peripheral blood samples,to predict the interaction targets of lncRNA-miRNA and miRNA-mRNA.The competitive endogenous RNA regulatory network was constructed using cytoscape software.RESULTS AND CONCLUSION:Differential expression analysis identified 127 differentially expressed lncRNAs and 921 differentially expressed mRNAs from the samples of alcohol-induced osteonecrosis of the femoral head.Then,through target gene prediction,205 miRNAs and 5184 mRNA targets were predicted,and finally the competing endogenous RNA network containing 3 lncRNAs(SNHG3,MUC19,LINC00476),5 miRNAs(hsa-miR-146b-5p,hsa-miR-139-5p,hsa-miR-126-3p,hsa-miR-193a-3p,hsa-miR-135a-5p),and 11 mRNAs(PEX5,ACTR3B,CHMP4B,CSMD1,MTRF1,ZNF3,HTR7,NR5A2,SYT14,CASK,ING5)was constructed,involved in stem cell differentiation,inflammatory response,neuroendocrine,gene polymorphism,and other biological processes.To conclude,a series of potential biomarkers of alcohol-induced osteonecrosis of the femoral head have been screened out by constructing the competing endogenous RNA network,which provides new ideas for further research on its molecular mechanism and therapeutic targets.