Identification of autophagy-related genes in neuropathic pain through bioinformatic analysis

Hereditas. 2023 Mar 1;160(1):8. doi: 10.1186/s41065-023-00269-w.

Abstract

Background: Neuropathic pain (NP) is one of the most common types of chronic pain and significantly compromises the quality of life. Autophagy is an intracellular catabolic process that is required to maintain cellular homeostasis in response to various stresses. The role of autophagy-related genes in the diagnosis and treatment of neuropathic pain remains unclear.

Methods: We identified autophagy-related differentially expressed genes (ARDEGs) and differentially expressed miRNAs (DE-miRNAs) in neuropathic pain by bioinformatics analysis of the GSE145226 and GSE145199 datasets. These ARDEGs and their co-expressed genes were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GSEA) and friends analysis. Meanwhile, we constructed TFs-ARDEGs, miRNA-ARDEGs regulatory network through ChIPBase database and the HTFtarget database, multiMir R package. Finally, we performed immune infiltration analysis of ARDEGs by Single Sample Gene Set Enrichment Analysis (ssGSEA).

Results: We identified 2 potential autophagy-related differentially expressed genes (Sirt2 and ST7) that may be closely associated with the pathogenesis of neuropathic pain. GO, KEGG and GSEA analysis revealed that these two ARDEGs were mainly enriched in pyridine nucleotide metabolic process, nicotinamide nucleotide metabolic process, Nicotinate and nicotinamide metabolism, NF-κB pathway, KRAS signaling, P53 pathway. In the TFs-ARDEGs and miRNA-ARDEGs regulatory network, miR-140-5p and Cebpb were predicted to be as crucial regulators in the progression of NP. For the ssGSEA results, Sirt2 was positively correlated with Eosinophil and Effector memory CD8+ T cell infiltration, which suggested that it may be involved in the regulation of neuroimmune-related signaling.

Conclusion: Two autophagy-related differentially expressed genes, especially Sirt2, may be potential biomarkers for NP, providing more evidence about the crucial role of autophagy in neuropathic pain.

Keywords: Autophagy; Bioinformatic analysis; Neuropathic pain; Sirt2.

MeSH terms

  • Autophagy / genetics
  • Computational Biology
  • Humans
  • MicroRNAs* / genetics
  • Neuralgia* / genetics
  • Niacinamide
  • Nucleotides
  • Quality of Life
  • Sirtuin 2

Substances

  • Sirtuin 2
  • MicroRNAs
  • Niacinamide
  • Nucleotides
  • Mirn140 microRNA, human