Transcriptional Profiling Uncovers Biologically Significant RNAs and Regulatory Networks in Nucleus Pulposus from Intervertebral Disc Degeneration Patients

Abstract

Objective. This study aimed to uncover biologically significant RNAs in nucleus pulposus tissues of human intervertebral disc degeneration (IVDD) by integrated transcriptional profiling. Methods. From the Gene Expression Omnibus (GEO) database, three IVDD-related microarray profiling datasets were retrieved and assessed by intragroup data repeatability test. Then, differentially expressed circRNAs, lncRNAs, mRNAs, and miRNAs were screened in nucleus pulposus tissues between IVDD and control samples via the limma package. Coexpression networks were separately conducted via weighted gene correlation network analysis (WGCNA). Based on the feature RNAs in the IVDD-related modules, IVDD-related circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA networks were conducted. The differentially expressed mRNAs in the two networks were analyzed by protein-protein interaction (PPI) and functional enrichment analyses. Results. By the intragroup data repeatability test, outlier samples were removed. Abnormally expressed RNAs were separately identified in nucleus pulposus between IVDD and controls. Via WGCNA, IVDD-related coexpression modules were constructed and the feature circRNAs, lncRNAs, mRNAs, and miRNAs were identified. Then, the circRNA- and lncRNA-miRNA-mRNA networks were built for IVDD. These mRNAs in the network exhibited complex interactions. Moreover, they were involved in distinct IVDD-related biological processes and pathways such as transcription, cell proliferation, TNF, TGF-β, and HIF signaling pathways. Conclusion. This study revealed biologically significant noncoding RNAs and their complex regulatory networks for IVDD.