Background:
Spinal cord injury (SCI) is a severe neurological deficit affecting both young and older people worldwide. The potential role of key
enhancer RNAs (
eRNAs) in SCI remains elusive, which is a prominent challenge in the
trauma repair process. This study aims to investigate the roles of key
eRNAs,
transcription factors (TFs), signaling pathways, and small-molecule inhibitors in SCI using multi-omics bioinformatics analysis. Methods: Microarray data of peripheral blood mononuclear cell (PBMC) samples from 27 healthy volunteers and 25 chronic-phase SCI patients were retrieved from the Gene Expression Omnibus database. Differentially expressed
transcription factors (DETFs), differentially expressed
enhancer RNAs (DEeRNAs), and differentially expressed target genes (DETGs) were identified using the Linear Models for Microarray Data (limma) package. Fraction of immune cells was estimated using CIBERSORT algorithm. Gene Set Variation Analysis (GSVA) was applied to identify the downstream signaling pathways. The eRNA regulatory network was constructed based on the correlation results. Connectivity Map (CMap) database was used to find potential drugs for SCI patients. The cellular communication analysis was performed to explore the molecular regulation mechanism of SCI based on single-cell
RNA sequencing (
scRNA-seq) data.
Chromatin immunoprecipitation sequencing (ChIP-seq) and Assay for
Transposase-Accessible
Chromatin using sequencing (ATAC-seq) data were used to validate the key regulatory mechanisms.
scRNA-seq dataset was used to validate the cell subtype localization of the key
eRNAs. Results: In total, 21 DETFs, 24 DEeRNAs, and 829 DETGs were identified. A regulatory network of 13 DETFs, six DEeRNAs, seven DETGs, two hallmark pathways, two immune cells, and six immune pathways was constructed. The link of
Splicing factor proline and
glutamine rich (SFPQ) (TF) and vesicular overexpressed in
cancer prosurvival
protein 1 (VOPP1) (eRNA) (R = 0.990, p < 0.001, positive), VOPP1 (eRNA) and
epidermal growth factor receptor (EGFR) (target gene) (R = 0.974, p < 0.001, positive), VOPP1, and T helper (Th) cells (R = -0.987, p < 0.001, negative), and VOPP1 and hallmark coagulation (R = 0.937, p < 0.001, positive) was selected.
Trichostatin A was considered the best compound target to SCI-related
eRNAs (specificity = 0.471, p < 0.001). Conclusion: VOPP1, upregulated by SFPQ, strengthened the transient expression of EGFR. Th cells and coagulation were the potential downstream pathways of VOPP1. This regulatory network and potential inhibitors provide novel diagnostic
biomarkers and therapeutic targets for SCI.