Abstract
OBJECTIVE: The aim of this study is to find potential biomarkers and drugs in intrahepatic cholestasis of pregnancy (ICP) by combining bioinformatics and experimental validation strategies. METHOD: Differentially expressed genes were obtained by analyzing the GSE282182 GEO dataset, after which the weighted gene co-expression network analysis was performed. The intersection of these two analyses yielded core genes. The MCODE module was used to analyze and identify key genes for further study, including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and immune infiltration analysis. Potential target drugs for the above target genes were obtained from the Comparative Toxicogenomics Database. Finally, external database validation and cell experiment validation were performed. RESULTS: A total of 10 core genes (RPS15A, RPL37A, RPL34, RPL32, RPS27, RPL23, RPS7, RPS27A, TPT1) were selected. GO and KEGG pathway analysis showed that they mainly participate in DNA repair, oxidative stress. The drug database showed that aspirin is linked to most genes. Verification of the external database proved that RPL34 was highly expressed in ICP, with statistically significant differences. In vitro cell experiments have confirmed that the expression levels of RPL34 and the activity of mitochondrial complex I were significantly reduced in human trophoblast cells by taurine intervention. Different concentrations of aspirin intervention can rescue apoptosis, restored mitochondrial complex I activity, and upregulated RPL34 expression via modulation of oxidative stress pathways. CONCLUSION: This study identified 10 core genes, and the relationship between RPL34 and ICP was found to warrant further investigation. As a drug targeting RPL34, aspirin may represent a potential therapeutic agent for treating ICP.