Potential Role of lncRNAs in Contributing to Pathogenesis of Intervertebral Disc Degeneration Based on Microarray Data
Yu Chen, Haijian Ni, Yingchuan Zhao, Kai Chen, Ming Li, Cheng Li, Xiaodong Zhu, Qiang Fu
Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai, China (mainland)
Med Sci Monit 2015; 21:3449-3458
Our study intended to identify potential long non-coding RNAs (lncRNAs) and genes, and to elucidate the underlying mechanisms of intervertebral disc degeneration (IDD).
MATERIAL AND METHODS: The microarray of GSE56081 was downloaded from the Gene Expression Omnibus database, including 5 human control nucleus pulposus tissues and 5 degenerative nucleus pulposus tissues, which was on the basis of GPL15314 platform. Identification of differentially expressed lncRNAs and mRNAs were performed between the 2 groups. Then, gene ontology (GO) and pathway enrichment analyses were performed to analyze the biological functions and pathways for the differentially expressed mRNAs. Simultaneously, lncRNA-mRNA weighted coexpression network was constructed using the WGCNA package, followed by GO and KEGG pathway enrichment analyses for the genes in the modules. Finally, the protein-protein interaction (PPI) network was visualized.
RESULTS: A total of 135 significantly up- and 170 down-regulated lncRNAs and 2133 significantly up- and 1098 down-regulated mRNAs were identified. Additionally, UBA52 (ubiquitin A-52 residue ribosomal protein fusion product 1), with the highest connectivity degree in PPI network, was remarkably enriched in the pathway of metabolism of proteins. Eight lncRNAs – LINC00917, CTD-2246P4.1, CTC-523E23.5, RP4-639J15.1, RP11-363G2.4, AC005082.12, MIR132, and RP11-38F22.1 – were observed in the modules of lncRNA-mRNA weighted coexpression network. Moreover, SPHK1 in the green-yellow module was significantly enriched in positive regulation of cell migration.
CONCLUSIONS: LncRNAs LINC00917, CTD-2246P4.1, CTC-523E23.5, RP4-639J15.1, RP11-363G2.4, AC005082.12, MIR132, and RP11-38F22.1 were differentially expressed and might play important roles in the development of IDD. Key genes, such as UBA52 and SPHK1, may be pivotal biomarkers for IDD.
Keywords: Cell Movement, Biomarkers - metabolism, Databases, Genetic, Down-Regulation, Gene Expression Profiling, Gene Expression Regulation, gene ontology, Intervertebral Disc Degeneration - genetics, Oligonucleotide Array Sequence Analysis, Protein Interaction Mapping, RNA, Long Noncoding - genetics, RNA, Messenger - metabolism