The Role of Gene Expression Changes in ceRNA Network Underlying Ossification of Ligamentum Flavum Development.

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.