School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, 710061, P.R. China.
Department of Knee Joint, Xi'an Hong Hui Hospital, Xi'an, 710054, P.R. China.
Sci Rep. 2017 Dec 14;7(1):17553. doi: 10.1038/s41598-017-17875-0.
Kashin-Beck disease (KBD) is a deformative, endemic osteochondropathy involving degeneration and necrosis of growth plates and articular cartilage. The pathogenesis of KBD is related to gene expression and regulation mechanisms, but long noncoding RNAs (lncRNAs) in KBD have not been investigated. In this study, we identified 316 up-regulated and 631 down-regulated lncRNAs (≥ 2-fold change) in KBD chondrocytes using microarray analysis, of which more than three-quarters were intergenic lncRNAs and antisense lncRNAs. We also identified 232 up-regulated and 427 down-regulated mRNAs (≥ 2-fold change). A lncRNA-mRNA correlation analysis combined 343 lncRNAs and 292 mRNAs to form 509 coding-noncoding gene co-expression networks (CNC networks). Eleven lncRNAs were predicted to have cis-regulated target genes, including NAV2 (neuron navigator 2), TOX (thymocyte selection-associated high mobility group box), LAMA4 (laminin, alpha 4), and DEPTOR (DEP domain containing mTOR-interacting protein). The differentially expressed mRNAs in KBD significantly contribute to biological events associated with the extracellular matrix. Meanwhile, 34 mRNAs and 55 co-expressed lncRNAs constituted a network that influences the extracellular matrix. In the network, FBLN1 and LAMA 4 were the core genes with the highest significance. These novel findings indicate that lncRNAs may play a role in extracellular matrix destruction in KBD.
大骨节病（KBD）是一种变形性、地方性骨软骨病，涉及生长板和关节软骨的退行性和坏死。KBD 的发病机制与基因表达和调控机制有关，但 KBD 中的长非编码 RNA（lncRNA）尚未得到研究。在这项研究中，我们使用微阵列分析在 KBD 软骨细胞中鉴定出 316 个上调和 631 个下调的 lncRNA（≥2 倍变化），其中超过四分之三是基因间 lncRNA 和反义 lncRNA。我们还鉴定出 232 个上调和 427 个下调的 mRNA（≥2 倍变化）。lncRNA-mRNA 相关性分析结合了 343 个 lncRNA 和 292 个 mRNA，形成了 509 个编码-非编码基因共表达网络（CNC 网络）。11 个 lncRNA 被预测为具有顺式调节靶基因，包括 NAV2（神经元导航 2）、TOX（胸腺细胞选择相关高迁移率族框）、LAMA4（层粘连蛋白，α4）和 DEPTOR（DEP 结构域包含 mTOR 相互作用蛋白）。KBD 中的差异表达 mRNA 显著有助于与细胞外基质相关的生物学事件。同时，34 个 mRNA 和 55 个共表达 lncRNA 构成了一个影响细胞外基质的网络。在网络中，FBLN1 和 LAMA4 是具有最高意义的核心基因。这些新发现表明，lncRNA 可能在 KBD 细胞外基质破坏中发挥作用。
