Identification of crucial miRNAs and lncRNAs for ossification of ligamentum flavum

Abstract

The present study aimed to screen crucial micro (mi)RNAs and long non-coding (lnc)RNAs involved in the development of ossification of ligamentum flavum (OLF) based on the miRNA-mRNA and lncRNA-miRNA-mRNA competing endogenous (ce)RNA regulatory network analyses, which are rarely reported. The differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs) and differentially expressed miRNAs (DEMs) between 4 OLF and 4 healthy controls were identified using two microarray datasets GSE106253 and GSE106256 collected from the Gene Expression Omnibus database. A protein-protein interaction (PPI) network was constructed, followed by calculation of topological characteristics and sub-module analysis in order to obtain hub DEGs. The miRNA-mRNA and lncRNA-miRNA networks that were established based on their interaction pairs, obtained from miRwalk and starBase databases, respectively, were integrated to form the ceRNA network. The underlying functions of mRNAs were predicted using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The present study screened 828 DEGs, 119 DELs and 81 DEMs between OLF and controls. PPI network and module analyses identified interleukin (IL)10, adenylate cyclase (ADCY)5, suppressor of cytokine signaling (SOCS)3, G protein subunit gamma (GNG) 4, collagen type II α 1 chain (COL2A1) and collagen type XIII α 1 chain (COL13A1) as hub genes. The miRNA-mRNA network analysis demonstrated IL10 could be regulated by miR-210-3p, while COL13A1 and COL2A1 could be modulated by miR-329-3p and miR-222-5p, respectively. lncRNA-miRNA-mRNA ceRNA network analysis identified that small nucleolar RNA host gene 16-hsa-miR-196a-5p-SOCS3, ankyrin repeat and SOCS box containing 16-AS1-hsa-miR-379-5p-GNG4, nuclear enriched abundant transcript 1-has-miR-181b-5p-ADCY5, rhophilin 1-AS1-hsa-miR-299-3p-WNT7B interaction axes may be crucial. DAVID analysis predicted IL10, ADCY5, GNG4 and SOCS3 were involved in ‘adaptive immune response’, ‘Chemokine signaling pathway’ and ‘regulation of apoptosis’ processes, while COL2A1, COL13A1 and WNT7B may be ossification related. In conclusion, the identification of these crucial miRNAs and lncRNAs may be conducive for explaining the pathogenesis of OLF and provide certain natural, endogenous and nontoxic drug targets for the treatment of OLF.