MicroRNA Expression Profiles, Target Genes, and Pathways in Intervertebral Disk Degeneration: A Meta-Analysis of 3 Microarray Studies.

ABSTRACT

BACKGROUND: Determining the expression profile and target genes of microRNA (miRNA) would assist in determining the pathophysiologic pathways in intervertebral disk degeneration (IDD). The aim of this study was to determine the expression profile of miRNA in degenerated intervertebral disks compared with normal healthy intervertebral disks. METHODS: We conducted a meta-analysis of 3 available miRNA expression datasets to identify a panel of co-deregulated miRNA genes and overlapping biological processes in IDD. Degenerated intervertebral disks were compared with normal healthy disks. We selected 35 miRNA features common to all 3 platforms. Then, we calculated differential expression P values from our unpaired data using metaMA package in R statistical software according to the moderated t test method (Limma). Based on the P values (where the threshold was <0.05), a list of differentially expressed miRNAs was identified. RESULTS: After normalization and selection of common miRNA features across all 3 platforms, we found a total of 5 differentially expressed miRNAs, among which miR-574-3p, miR-199a-5p, and miR-483-5p were not identified in any individual studies. Our results revealed that miR-199a-5p, miR-574-3p, miR-551a, and miR-640 are commonly upregulated in IDDs compared with control disks, whereas miR-483 is commonly downregulated. Pathway analysis of identified dysregulated miRNAs indicated the involvement of extracellular matrix-receptor interaction, adherens junction, and transforming growth factor-beta signaling pathway in the pathogenesis of IDDs. Moreover, the network of predicted targets for these miRNAs identified most affected target genes as ERBB4 and CLTC. CONCLUSIONS: We found that the identified miRNAs through meta-analysis are candidate predictive markers for IDDs through different pathways.