MiRNA-4769-5p/MBP and miRNA-1827/AR as key components in intervertebral disc degeneration: A network-based analysis approach

Abstract

Intervertebral disc degeneration (IDD) is a common cause of low back pain and disability. Standard treatment of IDD is conservative therapies and surgical treatment, that have some limitations including low success rate. Therefore, there is a high demand for novel and more effective treatments which target the molecular mechanisms of the disease. The aim of present study was the identification of key miRNAs and target genes involved in intervertebral disc degeneration using a network-based analysis approach. Two datasets of miRNA and mRNA microarray profiling was obtained from gene expression omnibus (GEO) and analyzed using ExAtlas and GEO2R to find differentially expressed miRNAs and genes, respectively. Functional annotation was performed in DAVID database and miEAA tool. Protein-protein interaction network (PPIN) was created in STRING and analyzed using Cytoscape. MicroRNA target prediction was done using miRWalk database. Overlapping genes was identified using Venn diagram. Overall, 320 differentially expressed genes (DEGs) and 14 differentially expressed miRNAs with 1323 predicted targets was selected. Some gene ontology and pathway enriched terms were glycosaminoglycan binding, neutrophil degranulation, extracellular matrix organization, immune system, cell cycle, GTPase activity and MAPK signaling. Twenty-eight and 90 hub genes were identified after analyzing DEGs network and predicted miRNAs targets network, respectively. DEGs and targets networks had 5 and 4 clusters/functional module, respectively. Two hub genes of AR and MBP were common between networks, which were the targets of hsa-miR-1827 and hsa-miR-4769-5p, respectively. These miRNAs/targets potentially are good candidates for diagnostic (biomarker) and therapeutic applications. However, this was only a in silico study and many in vitro, in vivo and clinical evidences are needed for validation.