基于全基因表达谱的骨关节炎软骨下骨转录因子预测及分析

摘要

Objective:To identify the master transcription factors(TF)that might be responsible for the gene expression alteration of OA.Methods:Raw expression data for rat OA model(GSE30322)was downloaded from NCBI GEO database.Mi-croarray data analysis for rat and human was carried out separately using functions from limma packagein R,gene expression was considered as significantly changed between conditions if adjusted P-value<0.05 and the absolute value of fold change≥2. iRegulon was applied to differentially up-regulated and down-regulated genes in OA separately.Results:(1)15 TFs,including FOXN4,NANOS1,E2F6,RAD21,MECOM,ETS1,MEF2A,POU2F3,BRCA1,GATA3,ZNF706,ZBTB33,SUZ12,DBP and SETDB1,were identified as the potential master TFs of up-regulated DEGs with statistical significance.(2)12 TFs,including ARID3A,YY1,RDBP,ATF1,CRX,TAF1,XBP1,SOX3,E2F4,PGR,TIMM8A and HOXA2,were identified as the potential master TFs of down-regulated DEGs with statistical significance. Conclusion:The newly identified TFs maybe play important roles in pathogenesis of early experimental osteoarthritis,and our study provides new diagnostic markers or therapeutic targets for OA.%目的:利用生物信息分析方法对骨关节炎软骨下骨全基因表达谱进行转录因子预测及分析.方法:下载基因芯片实验数据(GSE30322),使用软件包limma packagein R(版本:3.3.1)筛选差异表达基因,筛选差异基因的标准以基因表达上调或下调的倍数≥2为标准(P＜0.05),进一步使用Cytoscape软件(版本:3.4.0)的iRegulon插件预测分析调控这些差异表达基因的转录因子,并分析预测的转录因子所调控的差异表达基因.结果:发现上调的差异表达基因可能相关15个转录因子及其相对应的靶基因:FOXN4,NANOS1,E2F6,RAD21,MECOM,ETS1,MEF2A,POU2F3, BRCA1,GATA3,ZNF706,ZBTB33,SUZ12,DBP,SETDB1等.发现下调的差异表达基因可能相关12个转录因子及其相对应的靶基因:ARID3A,YY1,RDBP,ATF1,CRX,TAF1,XBP1,SOX3,E2F4,PGR,TIMM8A,HOXA2等.结论:预测分析的转录因子可能在骨关节炎软骨下骨致病机制调控中起了重要作用,其有可能成为新的防治骨关节炎的靶点.