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Bioinformatics analysis of ferroptosis in spinal cord injury

Neural Regeneration Research 2023年第3期18卷 626-633页

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 International Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina Department of Orthopedics Qilu Hospital of Shandong UniversityJinanShandong ProvinceChina Shandong University Centre for Orthopedics Advanced Medical Research InstituteCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina

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

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