首页|骨关节炎软骨中铁死亡相关微小RNA-信使RNA调控网络的构建及生物信息学分析

骨关节炎软骨中铁死亡相关微小RNA-信使RNA调控网络的构建及生物信息学分析

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目的 使用生物信息学方法构建铁死亡相关微小RNA(miRNAs)-信使RNA(mRNAs)的调控网络并探讨其在骨关节炎(OA)中的分子作用机制.方法 从基因表达综合数据库(GEO)下载软骨相关数据集GSE175961和GSE1140007,利用生物信息学方法筛选铁死亡相关miRNAs和mRNAs,并进行富集分析、miRNA-mRNA网络构建以及诊断价值分析.最后采用荧光实时定量聚合酶链反应(qRT-PCR)验证关键基因表达,并采用独立样本t检验比较其差异.结果 GSE175961数据集中共筛选获得了 15个差异表达miRNAs.使用TargetScan和miRDB数据库分别预测差异表达miRNAs的下游靶基因,共获得了 5 115个共存的靶基因.与GSE1140007数据集中19个差异表达铁死亡基因取交集后共获得了 4个下游铁死亡基因(PARP15、KLF2、CDKN1A、PDK4).基于上述研究结果构建了由15个差异表达的miRNAs和4个下游铁死亡基因组成的miRNA-mRNA调控网络.进一步富集分析表明,4个下游铁死亡基因与多种生物学功能和信号途径有关,如脂肪酸代谢、细胞周期调控、FOXO信号途径以及P53信号途径等.受试者工作曲线分析表明,4个下游铁死亡基因具有良好的诊断价值.此外,使用外部数据集证实,CDKN1A和PDK4在OA软骨组织中表达降低.而列线图表明,OA发生率随CDKN1A和PDK4表达降低而升高.qRT-PCR证实,正常组和OA组中,CDKN1A相对表达量分别为1.322±0.890、0.035±0.031;PDK4相对表达量分别为1.085±0.567、0.393±0.180.结论 本研究构建的铁死亡相关miRNA-mRNA调控网络与软骨退变密切相关.
Construction and bioinformatics analysis of ferroptosis related microRNA-messenger RNA regulato-ry network in osteoarthritis
Objective To establish the regulatory network between microRNA(miRNA)and mes-senger RNA(mRNA)associated with chondrocytes ferroptosis,and furterhmore investigate its molecular regulatory mechanism in the progression of osteoarthritis(OA)using bioinformatics analyses.Methods Cartilage degeneration related data sets including GSE175961 GSE1140007 were downloaded from the GeneExpression Omnibus(GEO)database,and then ferroptosis related miRNAs and mRNAs were screened.Functional and pathway enrichment analysis,construction of miRNA-mRNA regulatory network and diagnostic value analysis were performed.Finally,quantitative real time polymerase chain reaction(qRT-PCR)was used to confirm the expression of key genes,and independent t test was used to compare the differences.Results A total of 15 differentially expressed miRNAs were screened in the GSE175961 dataset.Furterhmore,TargetScan and miRDB databases were used to predict the differentially expressed downstream target genes of miRNAs,and 5115 co-existing target genes were obtained.A total of 4 down-stream ferroptosis related genes,including PARP15,KLF2,CDKN1A,PDK4,were then obtained after in-tersection with 19 differentially expressed ferroptosis related genes in the GSE114000 dataset.The miRNA-mRNA regulatory network consisted of 15 differentially expressed miRNAs and 4 downstream ferroptosis re-lated genes.Furterhmore enrichment analyses found that the 4 downstream ferroptosis genes were associated with a variety of biological functions and signaling pathways,such as fatty acid metabolism,cell cycle regu-lation,FOXO signaling pathway,and P53 signaling pathway.Moreover,receiver operating characteristic curve showed that these 4 genes had good diagnostic value in distinguishing OA and non-OA samples.In addition,an external data set confirmed that CDKN1A and PDK4 were reduced in OA cartilage.The nomo-gram model demonstrated a positive correlation between the incidence of OA and the downregulation of CDKN1A and PDK4.Finally,the results of real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)confirmed that the relative expression of CDKN1A in normal and OA groups was 1.322± 0.890 and 0.035±0.031,respectively.The relative expression of PDK4 was 1.085±0.567 and 0.393± 0.180,respectively.Conclusion The constructed miRNA-mRNA regulatory network associated with fer-roptosis is closely related to cartilage degeneration,thereby providing novel insights into the molecular mechanisms and treatment strategies for OA.

OsteoarthritisChondrocytesFerroptosisMicroRNAsMicroRNA-mRNA networkBioinformatics

孙红、陈坤浩、彭国璇、熊治林、李钟辉、邓进、杨华

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贵州医科大学附属医院骨科,贵阳 550004

贵州医科大学附属医院急诊外科,贵阳 550004

骨关节炎 软骨细胞 铁死亡 微小RNA 微小RNA-信使RNA调控网络 生物信息学分析

贵州省科技厅基础研究计划贵州省科技厅基础研究计划贵州省卫生健康委科学技术基金贵州省卫生健康委科学技术基金贵州省研究生科研基金项目贵州医科大学附属医院国家自然科学基金青年基金培育计划项目贵州医科大学附属医院国家自然科学基金青年基金培育计划项目

黔科合基础-ZK[2021]391黔科合基础-ZK[2023]一般344gzwjkj2020-1-120gzwkj2021-261YJSKYJJ[2021]157QKH-ZK[2021]391QKH-ZK[2023]344

2024

10.3760/cma.j.cn421213-20230926-00199

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子：0.759
ISSN：1001-9030
年,卷(期)：2024.41(1)
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