Chen Haitao, Chen Liaobin
Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Bone Joint Res. 2020 May 16;9(3):90-98. doi: 10.1302/2046-3758.93.BJR-2019-0140.R2. eCollection 2020 Mar.
This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network.
Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs.
We detected 1,212 DEmRNAs and 49 DElncRNAs in OA and normal knee cartilage. A total of 75 dysregulated lncRNA-miRNA interactions and 711 dysregulated miRNA-mRNA interactions were obtained in the ceRNA network, including ten DElncRNAs, 69 miRNAs, and 72 DEmRNAs. Similarly, 1,330 dysregulated lncRNA-mRNA interactions were used to construct the co-expression network, which included ten lncRNAs and 407 mRNAs. We finally identified seven hub lncRNAs, named MIR210HG, HCP5, LINC00313, LINC00654, LINC00839, TBC1D3P1-DHX40P1, and ISM1-AS1. Subsequent enrichment analysis elucidated that these lncRNAs regulated extracellular matrix organization and enriched in osteoclast differentiation, the FoxO signalling pathway, and the tumour necrosis factor (TNF) signalling pathway in the development of OA.
The integrated analysis of the ceRNA network and co-expression network identified seven hub lncRNAs associated with OA. These lncRNAs may regulate extracellular matrix changes and chondrocyte homeostasis in OA progress. 2020;9(3):90-98.
本研究旨在通过对竞争性内源RNA（ceRNA）网络和共表达网络的综合分析，揭示骨关节炎（OA）软骨中差异表达的关键长链非编码RNA（lncRNA）。
从基因表达综合数据库（GEO）（GSE114007）获取10例OA患者和10例正常人膝关节软骨组织的表达谱数据。使用edgeR软件包鉴定差异表达的信使RNA（DEmRNA）和lncRNA（DElncRNA）。我们将人类微小RNA（miRNA）-lncRNA/mRNA相互作用与DElncRNA/DEmRNA表达谱整合，构建ceRNA网络。同样，使用WGCNA软件包，利用lncRNA和mRNA表达谱构建共表达网络。基于ceRNA网络和共表达网络的综合分析鉴定潜在的关键lncRNA。使用StarBase和多实验矩阵数据库验证lncRNA。
我们在OA和正常膝关节软骨中检测到1212个DEmRNA和49个DElncRNA。在ceRNA网络中总共获得了75个失调的lncRNA-miRNA相互作用和711个失调的miRNA-mRNA相互作用，包括10个DElncRNA、69个miRNA和72个DEmRNA。同样，1330个失调的lncRNA-mRNA相互作用用于构建共表达网络，其中包括10个lncRNA和407个mRNA。我们最终鉴定出7个关键lncRNA，分别命名为MIR210HG、HCP5、LINC00313、LINC00654、LINC00839,、TBC1D3P1-DHX40P1和ISM1-AS1。随后的富集分析表明，这些lncRNA在OA发展过程中调节细胞外基质组织，并在破骨细胞分化、FoxO信号通路和肿瘤坏死因子（TNF）信号通路中富集。
ceRNA网络和共表达网络的综合分析鉴定出7个与OA相关的关键lncRNA。这些lncRNA可能在OA进展过程中调节细胞外基质变化和软骨细胞稳态。2020；9（3）：90-98。
