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. 2018 Aug;18(2):1504-1512.
doi: 10.3892/mmr.2018.9128. Epub 2018 Jun 5.

Comprehensive Evaluation of Differential lncRNA and Gene Expression in Patients With Intervertebral Disc Degeneration

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Free PMC article

Comprehensive Evaluation of Differential lncRNA and Gene Expression in Patients With Intervertebral Disc Degeneration

Zhigang Qu et al. Mol Med Rep. .
Free PMC article

Abstract

The present study aimed to identify novel intervertebral disc degeneration (IDD)‑associated long noncoding (lnc)RNAs and genes. The lncRNA and mRNA microarray dataset GSE56081 was downloaded from the Gene Expression Omnibus database and included 5 samples from patients with degenerative lumbar nucleus pulposus and 5 normal controls. Differentially expressed lncRNAs or differentially expressed genes (DEGs) were identified and co‑expression network analysis was performed followed by functional analysis for genes in the network. Additionally, a microRNA (miRNA)‑lncRNA‑mRNA competing endogenous RNA (ceRNA) regulatory network was constructed based on DEGs and lncRNAs in the co‑expression network. Furthermore, a literature search was performed to identify specific miRNAs that had been previously associated with IDD and a specific miRNA‑associated ceRNA network was extracted from the co‑expression network. A total of 967 genes and 137 lncRNAs were differentially expressed between IDD samples and controls. A co‑expression network was constructed and contained 39 differentially expressed lncRNAs and 209 DEGs, which were primarily involved in 'skeletal system development', 'response to mechanical stimulus' and 'bone development'. Furthermore, a ceRNA network was established, including 79 miRNAs, 9 downregulated lncRNAs and 148 DEGs. The identified miRNAs included a previously reported disease‑associated miRNA, hsa‑miR‑140. The present study demonstrated that hsa‑miR‑140 was regulated by three lncRNAs in the hsa‑miR‑140‑associated ceRNA network, including KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), OIP5 antisense RNA 1 (OIP5‑AS1) and UGDH antisense RNA 1 (UGDH‑AS1). KCNQ1OT1 was co‑expressed with neurochondrin (NCDN) and lon peptidase 2, peroxisomal. In addition, the lncRNAs OIP5‑AS1 and UGDH‑AS1 targeted several overlapping co‑expressed genes, including forkhead box F1 (FOXF1) and polycystin 1, transient receptor potential channel interacting (PKD1). Therefore, KCNQ1OT1 may regulate the expression of NCDN, and OIP5‑AS1 and UGDH‑AS1 may affect the expression of FOXF1 and PKD1 in IDD. Further experiments are required to validate the results of the present study, which may provide valuable insights into the identification of novel biomarkers associated with IDD.

Figures

Figure 1.
Figure 1.
Heatmaps of DEGs and differentially expressed lncRNAs. (A) Heatmap of DEGs between IDD and non-degenerative control samples. (B) Heatmap of differentially expressed lncRNAs between IDD and non-degenerative samples. Red color indicates upregulation and green color indicates downregulation. Normal and degenerated refer to samples obtained from non-degenerative controls and patients with IDD, respectively. DEGs, differentially expressed genes; lncRNA, long noncoding RNA; IDD, intervertebral disc degeneration.
Figure 2.
Figure 2.
lncRNA-mRNA co-expression network. Triangular and vee-shaped nodes represent upregulated and downregulated genes, respectively. Diamond-shaped and rectangular nodes indicate upregulated and downregulated lncRNAs, respectively. lncRNA, long noncoding RNA. Continuous line represents the connections between lncRNA and miRNA; dotted lines represent connections between miRNA and gene or lncRNA and gene.
Figure 3.
Figure 3.
Functional analysis of members of the long noncoding RNA-mRNA co-expression network. Bar plots presenting enriched (A) GO biological process terms and (B) Kyoto Encyclopedia of Genes and Genomes pathways in the co-expression network. The black line indicates-log10 (P-value). GO, Gene Ontology.
Figure 4.
Figure 4.
Construction of ceRNA network. Triangular and vee-shaped nodes denote upregulated and downregulated genes, respectively. Diamond-shaped nodes indicate downregulated long noncoding RNAs and rectangular nodes indicate miRNAs. ceRNA, competing endogenous RNA; miRNA/miR, microRNA.
Figure 5.
Figure 5.
Disease-specific competing endogenous RNA network. Pink and green circular nodes denote upregulated and downregulated genes, respectively. Green diamond-shaped nodes denote downregulated lncRNAs and red square nodes indicate intervertebral disc degeneration-associated miRNAs. Blue lines represent co-expression associations between lncRNAs and genes. Red lines indicate lncRNA-miRNA regulation associations. lncRNA, long noncoding RNA; miRNA, microRNA.

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References

    1. Vadalà G, Russo F, Ambrosio L, Papalia R, Denaro V. Mesenchymal stem cells for intervertebral disc regeneration. J Biol Regul Homeost Agents. 2016;30(4 Suppl 1):S173–S179. - PubMed
    1. Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: Pain and disc content. Nat Rev Rheumatol. 2014;10:44–56. doi: 10.1038/nrrheum.2013.160. - DOI - PMC - PubMed
    1. Gantenbein B, Illien-Jünger S, Chan SC, Walser J, Haglund L, Ferguson SJ, Iatridis C J, Grad S. Organ culture bioreactors-platforms to study human intervertebral disc degeneration and regenerative therapy. Curr Stem Cell Res Ther. 2015;10:339–352. doi: 10.2174/1574888X10666150312102948. - DOI - PMC - PubMed
    1. Colombier P, Clouet J, Hamel O, Lescaudron L, Guicheux J. The lumbar intervertebral disc: From embryonic development to degeneration. Joint Bone Spine. 2014;81:125–129. doi: 10.1016/j.jbspin.2013.07.012. - DOI - PubMed
    1. Yang W, Yu XH, Wang C, He WS, Zhang SJ, Yan YG, Zhang J, Xiang YX, Wang WJ. Interleukin-1β in intervertebral disk degeneration. Clin Chim Acta. 2015;450:262–272. doi: 10.1016/j.cca.2015.08.029. - DOI - PubMed

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