Ferroptosis related genes participate in the pathogenesis of spinal cord injury via HIF-1 signaling pathway

Brain Res Bull. 2023 Jan:192:192-202. doi: 10.1016/j.brainresbull.2022.11.010. Epub 2022 Nov 19.

Abstract

Background: Spinal cord injury (SCI) is a crushing disease without a effective and specific therapeutic strategy. Therefore, it is crucial to uncover underlying mechanism in order to identify potential treatments for SCI. Current studies show ferroptosis might pay important role in SCI.

Methods: In this study, we aimed to identify the key ferroptosis-related genes providing therapeutic targets for SCI. GSE45006, GSE19890 and GSE156999 from Gene Expression Omnibus (GEO) database were analyzed.

Results: A total of 61 ferroptosis-related DEGs were identified, followed by bioinformatics enrichment analyses and PPI network construction. Ten key ferroptosis-related genes were identified by Cytoscape (Cytohubba), most of which were enriched in the HIF-1 signaling pathway. Then we constructed a clip SCI rat model and qPCR was performed to assess the expressions of five genes enriched in HIF-1 signaling pathway (Stat3, Tlr4, Hmox1, Hif1a and Cybb). Finally, a ceRNA network, Stat3, Tlr4, Hmox1/miR127, miR383, miR485/rno-Mut_0003, rno-Pwwp2a_0002 was constructed and expression of mentioned molecules were validated by chip data.

Conclusions: Five hub genes from HIF-1 signaling pathway were identified and might play a central role in SCI, which indicated that ferroptosis was correlated with HIF-1 signaling pathway. These results can provide a new insight into molecular mechanisms and identify potential therapeutic targets for SCI.

Keywords: Bioinformatics; CeRNA network; Ferroptosis; HIF-1 signaling pathway; Spinal cord injury.

MeSH terms

  • Animals
  • Computational Biology / methods
  • Gene Expression Profiling / methods
  • Gene Regulatory Networks*
  • NADPH Oxidase 2 / metabolism
  • Rats
  • Signal Transduction / genetics
  • Spinal Cord Injuries* / genetics
  • Spinal Cord Injuries* / metabolism

Substances

  • Cybb protein, rat
  • NADPH Oxidase 2