We aimed at exploring the role of gene expression changes regulated by non-coding RNAs in ossification of ligamentum flavum (OLF). Three microarray datasets, including long non-coding RNA (lncRNA)/mRNA expression profile (GSE106253), circular RNA (circRNA) expression profile (GSE106255), and microRNA (miRNA) expression profile (GSE106256), were downloaded from the public Gene Expression Omnibus repository. The differentially expressed (DE) mRNAs, lncRNAs, miRNAs, and circRNAs in OLF tissues were analyzed, compared with normal tissues. Two competing endogenous RNA (ceRNA) networks with lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA interactions were constructed, separately. Random walk with the restart model was applied to calculate the correlations of mRNAs with the published OLF-related genes. The top 50 mRNAs were subjected to function enrichment analysis and active small-molecule prediction. Total 2323 DE mRNAs, 1168 lncRNAs, 336 circRNAs, and 29 miRNAs were identified based on the microarray datasets. The LncRNA-related ceRNA network was constructed with 614 lncRNA-miRNA, 494 miRNA-mRNA, and 2099 lncRNA-mRNA interaction pairs; the circRNA-related ceRNA network was constructed with 153 circRNA-miRNA, 190 miRNA-mRNA, and 210 circRNA-mRNA interaction pairs. There were 17 OLF-related genes retrieved from previous literature, such as NPPS, COL6A1, and COL11A2, among which COL6A1 was the overlapped gene with mRNAs in the ceRNA network. Subsequently, top 50 mRNAs that closely correlated with COL6A1 in the ceRNA network were captured and these genes were closely related with the collagen catabolic process, regulation of cell growth, and neuronal action potential. DRD1 and COL6A1 were predicted to be the targets by small active molecule drugs. The collagen catabolic process may be implicated in OLF development. COL6A1 and DRD1 may be the candidate targets for OLF. However, further validations were needed.

中文翻译：

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黄韧带骨化发展中的ceRNA网络中基因表达变化的作用。

我们旨在探讨由非编码RNA调节的基因表达变化在黄韧带骨化症（OLF）骨化中的作用。从公共基因表达库中下载了三个微阵列数据集，包括长非编码RNA（lncRNA）/ mRNA表达谱（GSE106253），环状RNA（circRNA）表达谱（GSE106255）和microRNA（miRNA）表达谱（GSE106256）。综合存储库。与正常组织相比，分析了OLF组织中的差异表达（DE）mRNA，lncRNA，miRNA和circRNA。分别构建了两个具有lncRNA-miRNA-mRNA和circRNA-miRNA-mRNA相互作用的竞争性内源RNA（ceRNA）网络。重新启动模型的随机游走被用于计算与已发布的OLF相关基因的mRNA的相关性。对前50个mRNA进行功能富集分析和活跃的小分子预测。根据微阵列数据集，共鉴定了2323个DE mRNA，1168个lncRNA，336个circRNA和29个miRNA。与LncRNA相关的ceRNA网络由614个lncRNA-miRNA，494个miRNA-mRNA和2099个lncRNA-mRNA相互作用对组成。用153个circRNA-miRNA，190个miRNA-mRNA和210个circRNA-mRNA相互作用对构建了circRNA相关的ceRNA网络。从以前的文献中检索到了17个OLF相关基因，例如NPPS，COL6A1和COL11A2，其中COL6A1是ceRNA网络中与mRNA重叠的基因。随后，在ceRNA网络中捕获了与COL6A1紧密相关的前50个mRNA，这些基因与胶原代谢过程，细胞生长调控，和神经元动作电位。小活性分子药物预测DRD1和COL6A1是靶标。胶原分解代谢过程可能与OLF发育有关。COL6A1和DRD1可能是OLF的候选目标。但是，需要进一步的验证。