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Identification and immune characteristics of N6-methyladenosine related ferroptosis-related genes in intervertebral

Zhen Che1, Ruibing Chen2, Ming Li3

  • 1Experimental Orthopedics and Trauma Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.

Scientific Reports
|September 29, 2025
PubMed

Insights

This study identifies ten key genes (HUBgenes) linked to intervertebral disc degeneration (IDD) by analyzing N6-methyladenosine (m6A) modification and ferroptosis-related genes (FRGs). ZNF595 and RRAS2 show significant upregulation in IDD, offering potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Ferroptosis plays a role in intervertebral disc degeneration (IDD).
  • N6-methyladenosine (m6A) modification is a major RNA modification, but its role in IDD via ferroptosis-related genes (FRGs) is underexplored.

Purpose of the Study:

  • To explore the key role of m6A-related ferroptosis-related genes (FRGs) in intervertebral disc degeneration (IDD).
  • To identify hub genes (HUBgenes) associated with IDD pathogenesis.
  • To investigate potential therapeutic targets for IDD.

Main Methods:

  • Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis.
  • Identification of m6A-FRGs related genes and intersection with differentially expressed genes (DEGs).
  • Least absolute shrinkage and selection operator (LASSO) for HUBgene identification, followed by gene set enrichment analysis (GSEA), immune cell abundance analysis, nomogram construction, and qRT-PCR validation.

Main Results:

  • 181 m6A-FRGs-DEGs were identified, leading to the selection of 10 HUBgenes (ZNF595, PLXDC1, FNBP1L, KLRB1, NRCAM, PPCDC, C9orf139, SIGLEC17P, RRAS2, and DPRXP4).
  • HUBgenes are involved in cytokine production and mitochondrial processes. Neutrophil abundance differed significantly between IDD and normal groups.
  • A nomogram based on ZNF595 and RRAS2 was constructed; ZNF595 and RRAS2 were validated as upregulated in IDD via qRT-PCR, with potential drug targets identified.

Conclusions:

  • Ten HUBgenes are significantly associated with intervertebral disc degeneration (IDD).
  • ZNF595 and RRAS2 are key upregulated genes in IDD, suggesting their vital role and potential as therapeutic targets.
  • This research provides evidence for the involvement of m6A-FRGs in IDD pathogenesis.
Keywords:
FerroptosisImmuneIntervertebral disc degenerationN6-methyladenosine

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