Construction of a novel mRNA-miRNA-lncRNA/circRNA triple subnetwork associated with immunity and aging in intervertebral disc degeneration.

Objective: Intervertebral disk degeneration (IVDD) is one of the most common causes of low back pain. However, in the etiology of IVDD, the specific method by which nucleus pulposus (NP) cell senescence and the immune response induce disease is uncertain.

Methods: Gene Expression Omnibus database was used to find differentially expressed genes (DEGs), differentially expressed miRNAs (DE miRNAs), differentially expressed lncRNAs (DE lncRNAs), and differentially expressed circRNAs (DE circRNAs). Functional enrichment analysis was performed through Enrichr database. Potential regulatory miRNAs, lncRNAs and circRNAs of mRNAs were predicted by ENCORI and circBank, respectively.

Results: We identified 198 upregulated and 131 downregulated genes, 39 upregulated and 22 downregulated miRNAs, 2152 upregulated and 564 downregulated lncRNAs, and 352 upregulated and 279 downregulated circRNAs as DEGs, DE miRNAs, DE lncRNAs, DE circRNAs, respectively. Functional enrichment analysis revealed that they were significantly enriched in Toll-like receptor signaling route and the NF-kappa B signaling pathway. An mRNA-miRNA-lncRNA/circRNA network linked to the pathogenesis of NP cells in IVDD was constructed based on node degree and differential expression level. Eight immune-related DEGs (6 upregulated and 2 downregulated genes) and five aging-related DEGs (3 upregulated and 2 downregulated genes) were identified in the critical network.

Conclusion: We established a novel immune-related and aging-related triple regulatory network of mRNA-miRNA-lncRNA/circRNA ceRNA, among which all RNAs may be utilized as the pathogenesis biomarker of NP cells in IVDD.