Key LncRNAs Associated With Oxidative Stress Were Identified by GEO Database Data and Whole Blood Analysis of Intervertebral Disc Degeneration Patients

Abstract

Background: Intervertebral disc degeneration (IDD) is a major cause of low back pain, but the onset and progression of IDD are unknown. Long non-coding RNA (lncRNA) has been validated to play a critical role in IDD, while an increasing number of studies have linked oxidative stress (OS) to the initiation and progression of IDD. We aim to investigate key lncRNAs in IDD through a comprehensive network of competing endogenous RNA (ceRNA) and to identify possible underlying mechanisms.Methods: We downloaded IDD-related gene expression data from the Gene Expression Omnibus (GEO) database and obtained differentially expressed-lncRNAs (DE-lncRNA), -microRNAs (DE-miRNA), and -messenger RNAs (DE-mRNA) by bioinformatics analysis. The OS-related lncRNA-miRNA-mRNA ceRNA interaction axis was constructed and key lncRNAs were identified based on ceRNA theory. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses on mRNAs regulated by lncRNAs in the ceRNA network. Single sample gene set enrichment analysis (ssGSEA) was used to reveal the immune landscape. Expression of key lncRNAs in IDD was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results: In this study, 111 DE-mRNAs, 20 DE-lncRNAs, and 502 DE-miRNAs were identified between IDD patients and controls, and 16 OS-related DE-lncRNAs were also identified. The resulting lncRNA-miRNA-mRNA network consisted of eight OS-related DE-lncRNA nodes, 24 DE-miRNA nodes, 70 DE-mRNA nodes, and 183 edges. Functional enrichment analysis suggested that the ceRNA network may be involved in regulating biological processes related to cytokine secretion, lipid, and angiogenesis. We also identified four key lncRNAs, namely lncRNA GNAS-AS1, lncRNA MIR100HG, lncRNA LINC01359, and lncRNA LUCAT1, which were also found to be significantly associated with immune cells.Conclusion: These results provide novel insights into the potential applications of OS-related lncRNAs in patients with IDD.

A concise review on the role of MIR100HG in human disorders

“…Being located in the cytoplasm, MIR100HG has been predicted to act as a competing endogenous RNA 38 . MIR100HG has also been among important lncRNAs that are linked with oxidative stress in the contetx of intervertebral disc degeneration 39 …”

“… 38 MIR100HG has also been among important lncRNAs that are linked with oxidative stress in the contetx of intervertebral disc degeneration. 39 …”