MiR-103a-3p与miR-107:骨关节炎进展过程中的潜在生物标志物

MiR-103a-3p and miR-107:potential biomarkers for the progression of osteoarthritis

目的探讨OA发病机制中潜在的Hub基因、关键miRNAs、生物过程及相关信号通路,为OA的发病机制及治疗提供生物信息学依据。方法从基因表达综合数据库(GEO)下载OA滑膜组织样本的表达谱芯片,鉴定差异表达基因DEGs,并进行功能富集分析。构建蛋白-蛋白相互作用网络(PPI),STRING和Cytoscape进行模块分析,进一步鉴定Hub基因,并对Hub基因进行更深一步的miRNAs挖掘。结果最终鉴定出与OA进展相关的9个Hub基因[细胞因子信号转导抑制因子(SOCS)3、转导素重复序列包含蛋白(BTRC)、F-框蛋白32(FBXO32)、KLHL22、UBE3A、HUWE1、UBR4、ANAPC5、TRIM50]和2个关键miRNAs(hsa-miR-103a-3P、hsa-miR-107),可能是OA发病机制中的潜在生物标志物。信号转导、RNA聚合酶Ⅱ启动子的转录正调控和蛋白丝氨酸/苏氨酸酶活性与OA的发病机制具有一定的相关性。此外,分析结果表明cAMP信号通路和Rap1信号通路也参与了OA的进展。结论潜在生物学分子、生物过程及相关通路对于OA的病因研究及治疗研究具有重要的指导意义。

Objective To explore the potential Hub genes,key miRNAs,biological processes and related signaling pathways in the pathogenesis of osteoarthritis(OA),and provide bioinformatics basis for the pathogenesis and treatment of OA.Methods The expression profiling chip of OA synovial tissue sample from Gene Expression Omnibus(GEO)were downloaded,differentially expressed genes(DEGs)were identified,and functional enrichment analysis was performed.A protein-protein interaction network(PPI)was constructed.STRING and Cytoscape was used for module analysis,and the Hub gene was further identified,and further miRNAs mining of the Hub gene was carried out.Results Finally,9 Hub genes(SOCS3,BTRC,FBXO32,KLHL22,UBE3A,HUWE1,UBR4,ANAPC5,TRIM50)and 2 key miRNAs(hsa-miR-103a-3P,hsa-miR-107)related to the progression of OA were identified.They might be potential biomarkers for the pathogenesis of OA.We also found that signal transduction,the transcriptional positive regulation of RNA polymeraseⅡpromoter,and protein serine/threoninase activity had a certain correlation with the pathogenesis of OA.In addition,our analysis results showed that cAMP signaling pathway and Rap1 signaling pathway were also involved in the progression of OA.Conclusion The potential biological molecules,biological processes and related pathways identified in this study may guide us for the further research on the etiology and treatment of OA.