A Transcriptome-Level Study Identifies Changing Expression Profiles for Ossification of the Ligamentum Flavum of the Spine

Abstract

Ossification of the ligamentum flavum (OLF) is a common spinal disorder that causes myelopathy and radiculopathy. Non-coding RNAs (ncRNAs) are involved in numerous pathological processes; however, very few ncRNAs have been identified to be correlated with OLF. Here we compared the expression of lncRNA, mRNA, circRNA, and microRNA in OLF tissues from OLF patients and healthy volunteers through mRNA, lncRNA, and circRNA microarrays and microRNA sequencing. A total of 2,054 mRNAs, 2,567 lncRNAs, 627 circRNAs, and 28 microRNAs (miRNAs) were altered during the process of OLF. qPCR confirmed the differential expression of selected mRNAs and ncRNAs. An lncRNA-mRNA co-expression network, miRNA-mRNA target prediction network, and competing endogenous RNA (ceRNA) network of circRNA-miRNA-mRNA were constructed based on a correlation analysis of the differentially expressed RNA transcripts. Subsequently, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for the differentially expressed mRNAs and the predicted miRNAs target genes were performed. In addition, a deregulated miRNA-19b-3p-based miRNA-circRNA-lncRNA-mRNA network was confirmed, by gain-of-function and loss-of-function experiments, to function in the process of ossification. Taken together, this study provides a systematic perspective on the potential function of ncRNAs in the pathogenesis of OLF. Keywords: non-coding RNA, ossification, ligamentum flavum, lncRNA, microRNA, circRNA, transcriptome