BackgroundIntervertebral Disc Degeneration (IDD) is a heterogeneous spinal disease whose underlying molecular mechanism is unclear.ObjectivesThis study aimed to identify, profile, and analyze microRNAs (miRNAs) related to IDD.MethodsMicroarray Gene Expression IDD data (GSE63492) were downloaded from Gene Expression Omnibus datasets. We employed Weighted Gene Co-Expression Network Analysis (WGCNA) to construct a miRNA co-expression network, and the miRNAs related to the IDD stage were detected. The number of differentially expressed miRNAs between normal and degenerated nucleus pulposus tissues was calculated. Twenty-three clinical specimens were used to validate the expression of miRNAs using qRT-PCR.ResultsWGCNA identified 48 miRNAs significantly related to the IDD stage, and 94 miRNAs that were significantly different between normal and degenerated nucleus pulposus tissues. We selected 32 overlapping miRNAs and identified 347 corresponding target genes. The integrative analysis revealed the biological function and pathways of these targeted genes. Analysis of clinical specimens validated that hsa-miR-4534 was upregulated in IDD, whereas hsa-miR-1827 and hsa-miR-185-5p were downregulated in IDD.ConclusionThis study has identified a subset of miRNAs that are related to IDD pathogenesis and hub miRNAs that are keys to the IDD co-expression network, which may potentially be utilized as indicators for treatment.