激素性股骨头坏死潜在失调基因的鉴定  

Identification of potential biomarkers of steroid-induced osteonecrosis of the femoral head

作　　者：黄涛[1] 崔泳[1] HUANG Tao;CUI Yong(Department of Orthopaedics,the Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学第五附属医院骨一科,乌鲁木齐830011

出　　处：《中华骨与关节外科杂志》2022年第1期55-62,共8页Chinese Journal of Bone and Joint Surgery

基　　金：新疆维吾尔自治区自然科学基金(2017D01C276);国家自然科学基金(81960396)。

摘　　要：目的:探讨与激素性股骨头坏死(SONFH)相关的潜在关键基因,为进一步研究SONFH提供有效的生物学信息。方法:从基因表达综合数据库(GEO)下载GSE74089和GSE123568的基因表达谱。使用Limma软件包鉴定差异表达基因(DEGs)。基于String数据库对蛋白质-蛋白质相互作用(PPI)网络进行分析,并对DEGs进行功能富集分析。构建mi RNA-m RNA相互作用的调控网络。在人骨髓间充质干细胞(BMSCs)中转染mi R-140-5p的模拟物和抑制剂以验证其对细胞的影响。结果:从GSE74089中筛选出569个DEGs。通过PPI网络识别364个DEGs具有互作关系。富集分析发现DEGs主要参与细胞外基质和细胞黏附分子等生物功能和信号通路。通过与GSE123568的DEGs交集分析识别出8个共同DEGs,利用受试者操作特征(ROC)曲线进一步识别SLC2A1、VCAN和FRY的临床诊断能力。通过定量聚合酶链反应验证了SLC2A1、VCAN和FRY在甲泼尼龙处理的BMSCs中的表达情况。预测分析结果中mi R-140-5p靶向调控SLC2A1,并通过细胞实验验证了靶向调控关系。结论:SLC2A1、VCAN和FRY可能是SONFH的潜在生物标志物。mi R-140-5p可能靶向SLC2A1调控HIF-1信号影响血管生成,并与SONFH的进展密切相关。Objective: To explore the potential key genes related to steroid-induced osteonecrosis of the femoral head(SONFH) and provide effective biological information for further study of SONFH. Methods: Gene expression profiles of GSE74089 and GSE123568 were downloaded from Gene Expression Omnibus(GEO) database. Differently expressed genes(DEGs) were identified by Limma package. The protein-protein interaction(PPI) network was analyzed based on String database, then the functional enrichment of DEGs was analyzed. Finally, the regulatory network of mi RNA-m RNA was constructed. In bone marrow mesenchyml stem cells(BMSCs), mimics and inhibitors of mi R-140-5p were transfected to verify their effects on cells. Results: A total of 569 DEGs were found in GSE74089 data. There were 364 DEGs included in PPI network. Enrichment analysis showed that DEGs were mainly involved in extracellular matrix and cell adhesion molecules and other biological functions. Eight DEGs were identified by the analysis of the intersection with the DEGs of GSE123568, and the clinical diagnosis ability of SLC2A1, VCAN and FRY was further identified by receiver operator characteristic(ROC) curve. Then the expression of SLC2A1, VCAN and FRY in BMSCs treated with methylprednisolone was confirmed by q PCR. In the predicted results, mi R-140-5p targeted to regulate SLC2A1, and the relationship between targeted regulation was verified by cell experiments. Conclusions:SLC2A1, VCAN and FRY may be potential biomarkers of SONFH. Mi R-140-5p may target SLC2A1 to regulate HIF-1 signal and affect angiogenesis, which is closely related to the progress of SONFH.

关 键 词：激素性股骨头坏死 差异表达基因 富集分析 

分 类 号：R681.8[医药卫生—骨科学]