骨关节炎软骨细胞衰老潜在生物标志物的筛选

Screening of potential biomarkers of chondrocyte senescence in osteoarthritis

摘要:

[目的] 采用生物信息分析学方法，筛选骨关节炎 （osteoarthritis, OA） 软骨细胞衰老潜在生物标志物，为揭示 OA 的发生机制及探索新的治疗方法提供理论依据。[方法] 从基因表达综合数据库 （gene expression omnibus, GEO） 获取 OA 软骨组织数据集， 使用 RStudio 软件筛选出差异表达基因 （differentially expressed genes, DEGs），并进行富集分析，再将 DEGs 与 SenMayo 衰老基因集取交集获得 Hub 基因，并进行验证，最后用 miRNet 在线平台及 Cytoscape 软件构建竞争性内源性 RNA （competing endogenous RNA, ceRNA） 网络。[结果] 数据集 GSE169077 和 GSE114007 经差异分析并取交集后共得到 DEGs 272 个；对 DEGs 行基因本体论 （Gene Ontology, GO） 分析，发现其主要富集在细胞外基质组织、细胞外结构组织等条目中；行京都基因与基因组百科全书（kyoto encyclopedia of genes and genomes, KEGG）分析，发现其主要富集在 PI3K-Akt 信号通路，黏着斑信号通路等；经筛选及验证，得到了 2 个 Hub 基因：IGF1 和 MMP2；构建 ceRNA 网络并筛选出 3 组 RNA 调控途径：KC- NQ1OT1/XIST- hsa- mir- 16- 5p- IGF1，KCNQ1OT1/XIST- hsa- mir- 424- 5p- MMP2，KCNQ1OT1/XIST- hsa- mir- 377- 3p- IGF1/ MMP2。[结论] IGF1 和 MMP2 可作为 OA 软骨细胞衰老的 Hub 基因，KCNQ1OT1/XIST-hsa-mir-16-5p-IGF1，KCNQ1OT1/ XIST-hsa-mir-424-5p-MMP2，KCNQ1OT1/XIST- hsa-mir-377-3p-IGF1/MMP2 可能是调节 OA 软骨细胞衰老的潜在 RNA 调控途径。

Abstract:

[Objective] To screen potential biomarkers associated with chondrocyte senescence in osteoarthritis (OA) by using bioinformatics analytics to provide a theoretical basis for unraveling the mechanisms of OA and exploring new therapeutic approaches. [Methods] The OA cartilage tissue datasets were downloaded from the Gene Expression Omnibus (GEO), and we used RStudio software to screen the deferentially expressed genes (DEGs) and perform enrichment analysis. Then, the DEGs were intersected with the SenMayo senescence gene set obtained to screen Hub genes, which were validated and identified. Finally, we used the miRNet online platform and Cytoscape software to construct the competitive endogenous RNA (ceRNA) network. [Results] A total of 272 DEGs were obtained from data sets GSE169077 and GSE114007 after difference analysis and intersection. The GO analysis showed that DEGs were mainly concentrated in extracellular matrix organization， extracellular structure organization, etc. The KEGG analysis showed that DEGs were mainly enriched in the PI3K-Akt signaling pathway, focal adhesion, etc. IGF1 and MMP2 were identified as the Hub genes. We constructed the ceRNA networks and screened out 3 groups of RNA regulatory pathways: KCNQ1OT1/XIST-hsa-mir-16-5p-IGF1, KCNQ1OT1/XIST-hsa-mir-424- 5p-MMP2, KCNQ1OT1/XIST-hsa-mir-377-3p-IGF1/MMP2. [Conclusion] IGF1 and MMP2 can act as the Hub genes of chondrocyte senescence in OA. KCNQ1OT1/XIST-hsa-mir-16-5p-IGF1, KCNQ1OT1/XIST-hsa-mir-424-5p-MMP2, KCNQ1OT1/XIST-hsa-mir377-3p-IGF1/MMP2 might be potential RNA regulatory pathways to regulate the chondrocyte Senescence of OA.