Comprehensive evaluation of differential lncRNA and gene expression in patients with intervertebral disc degeneration

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.

lncRNA/circRNA‑miRNA‑mRNA ceRNA network in lumbar intervertebral disc degeneration

“…It has been reported that TGFB promotes NP cell proliferation and stimulates ECM synthesis (11). Therefore, overexpression of TGFB may have the potential to inhibit IDD and exert therapeutic effects; this has been demonstrated in several in vivo studies (29,30).…”

“…These findings indicated that targeting the regulatory effects of associated lncRNAs, circRNAs, miRNAs and mRNAs may have a potential role in the clinical treatment of IDD. However, to the best of our knowledge, IDD-associated lncRNA/circRNA-miRNA-mRNA ceRNA regulatory mechanisms remain rarely reported, until now (11).…”

Reciprocal Regulation of TRPS1 and miR-221 in Intervertebral Disc Cells

“…The knowledge of specific key regulators that support the degenerative process from a molecular perspective should allow for not only better phenotyping of cells, but also developing new regenerative/reparative cell-based or biological therapies for this debilitating condition [3,4,5,31]. In recent years, research on gene expression modulation during both physiological and disease processes of IVD is focusing on attributing critical roles to transcription factors and non-coding RNAs (microRNAs and long non-coding RNAs), not only for what concerns their impact in diverse target genes, but also their interplay [32,33]. We focused here on this aspect and reported, for the first time, that the reciprocal regulation between the transcription factor TRPS1 and miR-221 seems to be of crucial importance for the maintenance of the IVD homeostasis and disc cell functions.…”

Comprehensive evaluation of differential long non‑coding RNA and gene expression in patients with cartilaginous endplate degeneration of cervical vertebra

“…The significant items in the results of enrichment analyses in the present study included 'integrin binding', 'ossification', 'ECM' and 'skeletal system development' Li et al (35) previously reported that the loss of OPG leads to the occurrence of IDD by promoting the 'ossification' biological process of the cartilage endplate in the osteoprotegerin (OPG)-knockout mice. Qu et al (36) reported that DEGs were primarily involved in 'skeletal system development' in a co-expression network in IDD and serve an important role the pathobiology of the disease. A, Genes whose microarray results are consistent with those reported in the literature; B, Genes whose microarray results are inconsistent with those reported in the literature.…”

“…Previous studies have reported that the ceRNA mechanism can be used for the analysis of multiple diseases ( 36 , 57 ). Qu et al ( 36 ) constructed a miRNA-lncRNA-mRNA ceRNA regulatory network on the basis of DEGs and lncRNAs in patients with IDD.…”