Bioinformatics analysis of ferroptosis in spinal cord injury  

作　　者：Jin-Ze Li Bao-You Fan Tao Sun Xiao-Xiong Wang Jun-Jin Li Jian-Ping Zhang Guang-Jin Gu Wen-Yuan Shen De-Rong Liu Zhi-Jian Wei Shi-Qing Feng 

机构地区：[1]International Cooperation Base of Spinal Cord Injury,Tianjin Key Laboratory of Spine and Spinal Cord Injury,Department of Orthopedics,Tianjin Medical University General Hospital,Tianjin,China [2]Department of Orthopedics,Qilu Hospital of Shandong University,Jinan,Shandong Province,China [3]Shandong University Centre for Orthopedics,Advanced Medical Research Institute,Cheeloo College of Medicine,Shandong University,Jinan,Shandong Province,China

出　　处：《Neural Regeneration Research》2023年第3期626-633,共8页中国神经再生研究（英文版）

基　　金：supported by National Key Research and Development Project of Stem Cell and Transformation Research,No.2019YFA0112100;Tianjin Key Research and Development Plan,Key Projects for Science and Technology Support,No.19YFZCSY00660(both to SQF)。

摘　　要：Ferroptosis plays a key role in aggravating the progression of spinal cord injury(SCI),but the specific mechanism remains unknown.In this study,we constructed a rat model of T10 SCI using a modified Allen method.We identified 48,44,and 27 ferroptosis genes that were differentially expressed at 1,3,and 7 days after SCI induction.Compared with the sham group and other SCI subgroups,the subgroup at 1 day after SCI showed increased expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 and the oxidative stress marker malondialdehyde in the injured spinal cord while glutathione in the injured spinal cord was lower.These findings with our bioinformatics results suggested that 1 day after SCI was the important period of ferroptosis progression.Bioinformatics analysis identified the following top ten hub ferroptosis genes in the subgroup at 1 day after SCI:STAT3,JUN,TLR4,ATF3,HMOX1,MAPK1,MAPK9,PTGS2,VEGFA,and RELA.Real-time polymerase chain reaction on rat spinal cord tissue confirmed that STAT3,JUN,TLR4,ATF3,HMOX1,PTGS2,and RELA mRNA levels were up-regulated and VEGFA,MAPK1 and MAPK9 mRNA levels were down-regulated.Ten potential compounds were predicted using the DSigDB database as potential drugs or molecules targeting ferroptosis to repair SCI.We also constructed a ferroptosis-related mRNA-miRNA-lncRNA network in SCI that included 66 lncRNAs,10 miRNAs,and 12 genes.Our results help further the understanding of the mechanism underlying ferroptosis in SCI.

关 键 词：bioinformatics drug ferroptosis Gene Ontology enrichment analysis gene-miRNA network Kyoto Encyclopedia of Genes and Genomes pathway mRNA-miRNA-lncRNA network progression spinal cord injury 

分 类 号：R651.2[医药卫生—外科学]