绝经后骨质疏松症差异microRNA表达及靶基因分析  

Differentially expressed microRNA and target gene analysis in patients with postmenopausal osteoporosis

作　　者：黄大耿 郝定均[1] 张峰[2] 贺宝荣[1] 孙宏慧 赵勤鹏[1] 刘翠翠[1] 王冀邯[1] Huang Dageng;Hao Dingjun;Zhang Feng;He Baorong;Sun Honghui;Zhao Qinpeng;Liu Cuicui;Wang Jihan(Department of Spine Surgery,Honghui Hospital,Xi'an Jiaotong University,Xi'an 710054,China;School of Public Health,Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]西安交通大学医学院附属红会医院脊柱外科,710054 [2]西安交通大学公共卫生学院,710061

出　　处：《中华创伤杂志》2019年第11期1038-1043,共6页Chinese Journal of Trauma

基　　金：国家自然科学基金(81702067);陕西省重点研发计划(2019SF-213);西安交通大学基本科研业务费自由探索与创新-教师类项目(xzy0120199130);陕西省卫生健康科研基金项目(2018E002)。

摘　　要：目的分析绝经后骨质疏松症(PMOP)女性外周血及骨组织中microRNA(miRNA)表达谱的变化,并对差异miRNA进行靶基因分析,为研究PMOP发病机制、筛选早期诊断标志物及骨质疏松性骨折的预防提供依据.方法获取公共数据平台NCBI-GEO DataSets中的PMOPmiRNA研究数据:第一组为GSE64433数据集,包含23例PMOP患者及25例对照者的外周血样本miRNA表达谱;第二组为GSE74209数据集,包含6例PMOP患者及6例对照者的股骨颈骨组织样本miRNA表达谱.运用R/Bioconductor进行数据处理及差异miRNA分析,筛选每组中PMOP与对照者间表达倍数改变>2,P<0.05的miRNA为组间差异表达miRNA.结合TargetScan、miRDB、miRTarBase数据库进行miRNA靶基因预测,选取在三个数据库中均存在的靶基因,运用Cytoscape绘制并分析miRNA-靶基因调控网络图.结果在第一组中(GSE64433数据集),PMOP外周血筛选出224个差异表达miRNA(75个上调miRNA,149个下调miRNA);在第二组中(GSE74209数据集),PMOP股骨颈骨组织中筛选出132个差异表达miRNA(58个上调miRNA,74个下调miRNA).将第一组及第二组中的差异miRNA取交集,得到8个miRNA在PMOP均呈下调改变,共调控327个靶基因,且其中10个靶基因受到两个miRNA的共同调控.结论PMOP miRNA-靶基因调控网络中的核心miRNA及受到多个miRNA共同调控的靶基因可能在其发病与进展中起到了一定的作用,有作为疾病分子标志物的潜在应用价值.这对PMOP的发生发展、诊断标志物筛选及骨质疏松性骨折预防等相关研究有重要意义.Objective To analyze the differentially expressed microRNA(miRNA)and their target genes in peripheral blood and bone tissue of postmenopausal osteoporosis(PMOP),and provide basis for the study of pathogenesis as well as biomarkers identification of PMOP.Methods Two miRNA datasets of PMOP from the public platform NCBI-GEO DataSets were obtained,including GSE64433(the miRNA expression profile of peripheral blood samples,including 23 PMOP patients and 25 controls)and GSE74209(the miRNA expression profile of the femoral neck bone tissue sample,including six PMOP patients and six controls).R/Bioconductor was performed for data analysis and differentially expressed miRNA screening,and miRNAs with fold change>2&P<0.05 between osteoporosis and controls were selected as differentially expressed miRNA.The miRNA target gene prediction was performed by combining TargetScan,miRDB and miRTarBase databases.The miRNA-target gene regulatory network was constructed and analyzed by Cytoscape.Results There were 224 differentially expressed miRNAs(75 up-regulated miRNAs and 149 down-regulated miRNAs)in the peripheral blood samples of PMOP group(GSE64433 dataset)and 132 differentially expressed miRNAs(58 up-regulated miRNAs and 74 down-regulated miRNAs)in the femoral neck bone tissue of PMOP group(GSE74209 dataset).We combined the results from the two datasets and obtained 8 miRNAs down-regulated in both datasets,and the 8 miRNAs regulated a total of 327 target genes,and 10 of these target genes were co-regulated by two miRNAs.Conclusions The core miRNAs and the target genes regulated by multiple miRNAs in the regulatory network may play important roles in the pathogenesis of PMOP and have potential application values as molecular biomarkers of disease.These findings are meaningful for the studies of PMOP pathogenesis,biomarkers screening and prevention of osteoporotic fractures.

关 键 词：骨质疏松 绝经后 微RNAS 调控网络 

分 类 号：R73[医药卫生—肿瘤]