Dihydrolactate dehydrogenase (DHODH) may be a potential drug target for the treatment of lumbar disc herniation: a bioinformatics analysis based on mitochondria-related genes

Abstract

Abstract Objective: To explore mitochondrial metabolism-related genes as potential hub genes in lumbar disc herniation (LDH) and their associated molecular regulatory mechanisms, and to predict potential drug targets. Methods: Based on the mRNA-Seq data of mitochondrial metabolism genes and LDH from public databases, the hub genes were screened and their biological functions were investigated using LASSO regression analysis, support vector machine (SVM) algorithm and random forest (RF). Then, the immune profile of osteoporosis was detected based on the CIBERSORT algorithm to study the immune cell infiltration of the hub genes. The diagnostic model Nomogram risk prediction model is constructed and the effect is evaluated. Finally, potential drug targets were obtained and validated by molecular docking through drug database. Results: 4 hub genes were obtained:DHODH,BAK1,TIMM17B and TIMM23. The results of GO analysis mainly include mitochondrial function and composition,macromolecular transport such as Bcl-2 family proteins,heat shock protein binding,etc. KEGG pathway is mainly involved in multi-species apoptosis pathway,thyroid cancer,pyrimidine metabolism,etc. These four hub genes have correlation with a variety of immune cells, as well as constructing a diagnostic model with good diagnostic efficacy. Finally, through drug database screening and molecular docking validation, DHODH was found to have a potential role in the treatment of LDH by affecting pyrimidine metabolism. CONCLUSION: DHODH, BAK1, TIMM17B, and TIMM23 are hub genes associated with mitochondrial metabolism in LDH. They act on LDH through multiple pathways and may be hub genes for LDH diagnostic biomarkers. Finally, DHODH was found to be a potential drug target for the treatment of LDH.