Abstract
Objective: Intervertebral disc degeneration (IDD) is the major cause of low back pain. We aimed to identify the key genes for IDD pathogenesis. Methods: An integrated analysis of microarray datasets of IDD archived in public Gene Expression Omnibus was performed. Bioinformatics analyses including identification of differentially expressed mRNAs/microRNAs/long non-coding RNAs (DEMs/DEMis/DELs), pathway enrichment, and competitive endogenous RNA (ceRNA) network construction were performed to give insights into the potential functions of differentially expressed genes (DEGs, including DEMs, DEMis, and DELs). The diagnostic value of DEMis in distinguishing IDD from normal controls was evaluated through receiver operating characteristic (ROC) analysis. Results: DEGs were identified in IDD, including H19 and HOTAIR. In the DEMis–DEMs network of IDD, miR-1291, miR-4270, and miR-320b had high connectivity with targeted DEMs. Cell death biological processes and the JAK–STAT pathway were significantly enriched from targeted DEMs. The area under the curve (AUC) of 10 DEMs including miR-1273e, miR-623, miR-518b, and miR-1291 in ROC analysis was more than 0.8, which indicated that those 10 DEMs had diagnostic value in distinguishing IDD from normal individuals. Conclusions: DELs H19 and HOTAIR were related to IDD pathogenesis. Cell death biological processes and the JAK–STAT pathway might play key roles in IDD development.
Highlights
A series of articles displayed non-coding RNAs, such as circular RNAs, long non-coding RNAs, and microRNAs, are involved in the initiation and progression of Intervertebral disc degeneration (IDD). lncRNA HCG18 suppresses the growth of nucleus pulposus (NP) cells and promotes the IDD development through the miR-H19/HOTAIR Implicated in IDD
A total of four mRNA expression datasets including 52 healthy controls (HCs) and 31 IDD patients were used to identify the Differentially expressed mRNAs (DEMs) in IDD
A total of 1995 DEMs including 907 downregulated and 1,078 up-regulated DEMs were identified in IDD vs. HC
Summary
Spinal degenerative disease is a major health problem with a social burden worldwide. Intervertebral disc degeneration (IDD) is a major cause of back, neck, and radicular pain, which is characterized by the loss of nucleus pulposus cell (Waddell, 1996; Andersson, 1999; Ma et al, 2016). The intervertebral disc comprises an outer circumferential annulus fibrosus (AF) and an inner nucleus pulposus (NP), bordered by two cartilaginous endplates (Johnson et al, 2015). Author mRNA expression profiling (52 HC vs 31 IDD) GSE23130 17 8 GPL1352 [U133_X3P] Affymetrix Human X3P Array GSE15227 12 3 GPL1352 [U133_X3P] Affymetrix Human X3P Array GSE17077 9 10 GPL1352 [U133_X3P] Affymetrix Human X3P Array GSE70362 14 10 GPL17810 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array. Helen Gruber Helen Gruber Helen Gruber Peadar O’Gaora miRNA expression profiling (11 HC vs 11 IDD) 3 3 GPL20712 Agilent-070156 Human miRNA [miRNA version].
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