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.

miR‐342‐3p promotes osteogenic differentiation via targeting ATF3

“…Systemic variations between the expressions of miRNAs in four human OLF samples and four normal ligamentum flavum (LF) samples were previously identified using miRNA sequencing analysis , from which we noted that miR‐342‐3p was over‐expressed in OLF (Fig. A).…”

“…A). Systemic variations between the expression of mRNAs in four human ossified LF samples and four normal LF samples were previously identified using a microarray analysis , from which we noted that ATF3 was remarkably down‐regulated in ossified LF (Fig. B) (The microarray data have been uploaded to NCBI Gene Expression Omnibus and can be adopted by GEO Series accession number ).…”

Identification of crucial miRNAs and lncRNAs for ossification of ligamentum flavum

“…Therefore, lncRNAs may also be important targets for the treatment of OLF. However, OLF-related lncRNAs are rarely reported, with the exception of the a previous study by Han et al (22).…”

“…The aim of the present study was to use the datasets uploaded by Han et al (22) to further identify novel miRNAs and crucial lncRNAs for OLF based on the miRNA-mRNA and lncRNA-miRNA-mRNA ceRNA regulatory networks. The findings may provide insight for underlying therapeutic strategies for OLF by changing the expression levels of miRNAs and lncRNAs, which could in turn regulate the target genes.…”

Integrated analysis of a lncRNA‑mRNA network reveals a potential mechanism underlying necrotizing enterocolitis

“…long non-coding rnas (lncrnas) are autonomously transcribed non-coding rnas, which are >200 nucleotides in length (6). lncrnas can act at the transcriptional, post-transcriptional and epigenetic levels via cis-or trans-acting pathways (7,8). Previous studies have reported the potential importance of lncrnas in maintaining the intestinal barrier and mediating inflammatory lesions (9)(10)(11).…”