2. Academic Validation
  3. Ferroptosis related genes participate in the pathogenesis of spinal cord injury via HIF-1 signaling pathway

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.
Haoru Dong 1,  Chi Zhang 2,  Donglei Shi 3,  Xiao Xiao 4,  Xingyu Chen 5,  Yuanxiao Zeng 6,  Xiaomu Li 7,  Rong Xie 8
Affiliations

Affiliations

  • 1 Department of Neurosurgery; National Center for Neurological Disorders; Neurosurgical Institute of Fudan University; Shanghai Clinical Medical Center of Neurosurgery; Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: donghaoru@163.com.
  • 2 The First Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: zhangc0707@126.com.
  • 3 Department of Nursing, Huashan Hospital, Fudan University, Shanghai 200032, China. Electronic address: 463342147@qq.com.
  • 4 Department of Neurosurgery; National Center for Neurological Disorders; Neurosurgical Institute of Fudan University; Shanghai Clinical Medical Center of Neurosurgery; Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: xxiao.neuro-surg@outlook.com.
  • 5 Department of Neurosurgery; National Center for Neurological Disorders; Neurosurgical Institute of Fudan University; Shanghai Clinical Medical Center of Neurosurgery; Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: m15201736021@163.com.
  • 6 The First Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: ZengYX0207@163.com.
  • 7 Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: li_xiao_mu@163.com.
  • 8 Department of Neurosurgery; National Center for Neurological Disorders; Neurosurgical Institute of Fudan University; Shanghai Clinical Medical Center of Neurosurgery; Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Neurosurgery, National Regional Medical Center; Huashan Hospital Fujian Campus, Fudan University; The First Affiliated Hospital of Fujian Medical University, Fuzhou 350209, Fujian Province, China. Electronic address: rongxie@fudan.edu.cn.
PMID: 36414158 DOI: 10.1016/j.brainresbull.2022.11.010
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.

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