Exploration of biomarkers associated with histone lactylation modification in spinal cord injury

Author:

Sun Yisong1,Gao Jie2,Jing Juehua1

Affiliation:

1. The Second Affiliated Hospital of Anhui Medical University

2. The First Affiliated Hospital of Bengbu Medical University

Abstract

Abstract

Background The biological functions of histone lactylation (HLA) modification-related genes (HLMRGs) in spinal cord injury (SCI) are unknown. Therefore, we explored the expression and molecular mechanism of HLMRGs in SCI by bioinformatics means. Methods GSE151371, GSE47681, and 10 HLMRGs were incorporated in this study. Biomarkers were screened based on the receiver operating characteristic curves for the modeling of logistic regression and nomogram. Additionally, gene set enrichment analysis (GSEA) was executed to detect biomarkers’ functions. Samples were clustered based on biomarkers, identifying distinct groups. Differential expressed genes between these clusters were determined, and inter-cluster analyses of Hallmark pathways, HLA genes, and immune functions were conducted. Weighted gene co-expression network analysis (WGCNA) was used to select cluster-related module genes for protein-protein interaction (PPI) network construction, pinpointing key proteins. miRNA-TF-biomarker and drug-biomarker networks were established. Biomarker expression was validated using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results In GSE151371, 8 biomarkers (HDAC1, HDAC2, HDAC3, SIRT1, SIRT3, LDHA, LDHB, and GCN5 (KAT2A)) with AUC > 0.7 were significantly different expressed between SCI and control samples. 8 biomarkers were different expressed in 2 clusters. By differential expression analysis of cluster 1 versus cluster 2, enriched in ‘phosphatidylinositol signaling system’ etc. Finally, a miRNA-TF-biomarker network comprising eight biomarkers were constructed. The expression validation of eight biomarkers by RT-qPCR, LDHA were high expression, while HDAC3 and SIRT3 were low expression in SCI. Conclusion In summary, 8 biomarkers playing an important role in SCI were identified, which provided in-depth references for HLMRGs in SCI.

Publisher

Springer Science and Business Media LLC

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