Study and validation on mitochondrial and immune-related hub genes in gestational diabetes mellitus based on bioinformatics

Xin Zhao^*Yuehan MaJianbin SunZHANG XIAOMEI

• International Hospital, Peking University, Beijing, China

Background: Mitochondria and immune function are pivotal in pathogenesis of gestational diabetes mellitus (GDM). However, intricate molecular mechanisms underlying their involvement remain elusive. Hence, this study endeavors to elucidate intricate interaction of mitochondria-related genes (MRGs) and immune-related genes (IRGs) in GDM. Methods: In this study, GDM-related datasets (GSE103552, GSE154414 and GSE173193) were integrated along with MRGs and IRGs. Initially, differential expression analysis was conducted on GSE103552 to pinpoint differentially expressed genes (DEGs), which were then intersected with MRGs and IRGs. Correlation of intersection genes was assessed, and those with statistical significance and strong correlation were singled out as candidate genes. Subsequently, 3 machine learning algorithms were employed to further refine selection of signature genes. Optimal model was determined, and genes within this model were designated as signature genes. Following this, expression of signature genes were scrutinized, and those showing significant differences and consistent trends between GDM and control groups in GSE103552 and GSE154414 datasets were identified as hub genes. Further investigations encompassed exploring chromosomal and subcellular localization of hub genes. Enrichment analyses, regulatory mechanism, and drug prediction analyses were performed on hub genes to uncover their potential effects. Furthermore, The key cells were analyzed in GSE173193. Finally, the expression of hub genes was verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: Through a comprehensive analysis, MRPL15, MRPL22, and MRPS18C emerged as pivotal hub genes, displaying significantly lower expression levels in GDM group. Chromosome localization revealed MRPS18C on chromosome 4, MRPL22 on chromosome 5, and MRPL15 on chromosome 8. Furthermore, subcellular distribution analysis demonstrated that MRPL15 and MRPL22 were predominantly expressed in nucleus, whereas MRPS18C exhibited cytoplasmic localization. Enrichment analysis unveiled spliceosome, proteasome, Parkinson disease, and ribosome pathways were enriched by hub genes. YY1 regulated MRPS18C and MRPL22, ARID3A regulated MRPS18C and MRPL15, while FOXC1 regulated MRPL22 and MRPL15. Finally, results of RT-qPCR showed that MRPL15, MRPL22 and MRPS18C had obviously lower expression in GDM group. Conclusion: In conclusion, our findings highlighted significance of MRPL15, MRPL22, MRPS18C, monocytes and villous cytotrophoblast cells in GDM. These insights offered valuable implications for diagnosis and therapeutic interventions targeting GDM.