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

Overview

Journal Front Genet

Date 2022 Aug 8

PMID 35937989

Authors

Xueliang Jiang

Junfei Wu

Chunhui Guo

Wenhui Song

Affiliations

Soon will be listed here.

Abstract

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. 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). 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. These results provide novel insights into the potential applications of OS-related lncRNAs in patients with IDD.

Citing Articles

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References

Brandl A, Hartmann A, Bechmann V, Graf B, Nerlich M, Angele P . Oxidative stress induces senescence in chondrocytes. J Orthop Res. 2011; 29(7):1114-20. DOI: 10.1002/jor.21348. View

Gamez-Valero A, Guisado-Corcoll A, Herrero-Lorenzo M, Solaguren-Beascoa M, Marti E . Non-Coding RNAs as Sensors of Oxidative Stress in Neurodegenerative Diseases. Antioxidants (Basel). 2020; 9(11). PMC: 7695195. DOI: 10.3390/antiox9111095. View

Yeung M, Melgar S, Baranov V, Oberg A, Danielsson A, Hammarstrom S . Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune cell phenotype and TcR-gammadelta expression. Gut. 2000; 47(2):215-27. PMC: 1728017. DOI: 10.1136/gut.47.2.215. View

Wang Y, Dai G, Li L, Liu L, Jiang L, Li S . Transcriptome signatures reveal candidate key genes in the whole blood of patients with lumbar disc prolapse. Exp Ther Med. 2019; 18(6):4591-4602. PMC: 6862187. DOI: 10.3892/etm.2019.8137. View

Szklarczyk D, Gable A, Lyon D, Junge A, Wyder S, Huerta-Cepas J . STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2018; 47(D1):D607-D613. PMC: 6323986. DOI: 10.1093/nar/gky1131. View

Huang Y, Zhang C, Zhou Y . LncRNA MIR100HG promotes cancer cell proliferation, migration and invasion in laryngeal squamous cell carcinoma through the downregulation of miR-204-5p. Onco Targets Ther. 2019; 12:2967-2973. PMC: 6489621. DOI: 10.2147/OTT.S202528. View

Leimer E, Gayoso M, Jing L, Tang S, Gupta M, Setton L . Behavioral Compensations and Neuronal Remodeling in a Rodent Model of Chronic Intervertebral Disc Degeneration. Sci Rep. 2019; 9(1):3759. PMC: 6403208. DOI: 10.1038/s41598-019-39657-6. View

Wang H, Zhu Y, Cao L, Guo Z, Sun K, Qiu W . circARL15 Plays a Critical Role in Intervertebral Disc Degeneration by Modulating miR-431-5p/DISC1. Front Genet. 2021; 12:669598. PMC: 8255806. DOI: 10.3389/fgene.2021.669598. View

Sheng X, Guo Q, Yu J, Xu Y . Experimental research on the effect of microRNA-21 inhibitor on a rat model of intervertebral disc degeneration. Exp Ther Med. 2018; 16(1):67-72. PMC: 5995058. DOI: 10.3892/etm.2018.6156. View

10.

Xi Y, Jiang T, Wang W, Yu J, Wang Y, Wu X . Long non-coding HCG18 promotes intervertebral disc degeneration by sponging miR-146a-5p and regulating TRAF6 expression. Sci Rep. 2017; 7(1):13234. PMC: 5643303. DOI: 10.1038/s41598-017-13364-6. View

11.

Lee J, Song J, Baek M, Jung H, Kang H, Han I . Interleukin-1β induces angiogenesis and innervation in human intervertebral disc degeneration. J Orthop Res. 2010; 29(2):265-9. DOI: 10.1002/jor.21210. View

12.

Gabr M, Jing L, Helbling A, Sinclair S, Allen K, Shamji M . Interleukin-17 synergizes with IFNγ or TNFα to promote inflammatory mediator release and intercellular adhesion molecule-1 (ICAM-1) expression in human intervertebral disc cells. J Orthop Res. 2010; 29(1):1-7. PMC: 3007672. DOI: 10.1002/jor.21206. View

13.

Zhang S, Hu B, Liu W, Wang P, Lv X, Chen S . The role of structure and function changes of sensory nervous system in intervertebral disc-related low back pain. Osteoarthritis Cartilage. 2020; 29(1):17-27. DOI: 10.1016/j.joca.2020.09.002. View

14.

Li Z, Li X, Chen C, Li S, Shen J, Tse G . Long non-coding RNAs in nucleus pulposus cell function and intervertebral disc degeneration. Cell Prolif. 2018; 51(5):e12483. PMC: 6528936. DOI: 10.1111/cpr.12483. View

15.

Wang S, Ke H, Zhang H, Ma Y, Ao L, Zou L . LncRNA MIR100HG promotes cell proliferation in triple-negative breast cancer through triplex formation with p27 loci. Cell Death Dis. 2018; 9(8):805. PMC: 6057987. DOI: 10.1038/s41419-018-0869-2. View

16.

Roh E, Darai A, Kyung J, Choi H, Kwon S, Bhujel B . Genetic Therapy for Intervertebral Disc Degeneration. Int J Mol Sci. 2021; 22(4). PMC: 7914740. DOI: 10.3390/ijms22041579. View

17.

Paul S, Singh A, Shilpi , Lal G . Phenotypic and functional plasticity of gamma-delta (γδ) T cells in inflammation and tolerance. Int Rev Immunol. 2013; 33(6):537-58. DOI: 10.3109/08830185.2013.863306. View

18.

Li W, Ding Z, Zhang H, Shi Q, Wang D, Zhang S . The Roles of Blood Lipid-Metabolism Genes in Immune Infiltration Could Promote the Development of IDD. Front Cell Dev Biol. 2022; 10:844395. PMC: 8864150. DOI: 10.3389/fcell.2022.844395. View

19.

Zhang G, Deng Y, Xie Q, Ren E, Ma Z, He X . Sirtuins and intervertebral disc degeneration: Roles in inflammation, oxidative stress, and mitochondrial function. Clin Chim Acta. 2020; 508:33-42. DOI: 10.1016/j.cca.2020.04.016. View

20.

Tan C, Cao J, Chen L, Xi X, Wang S, Zhu Y . Noncoding RNAs Serve as Diagnosis and Prognosis Biomarkers for Hepatocellular Carcinoma. Clin Chem. 2019; 65(7):905-915. DOI: 10.1373/clinchem.2018.301150. View