Transcriptomic and metabolomic profiling reveal the p53-dependent benzeneacetic acid attenuation of silica‐induced epithelial–mesenchymal transition in human bronchial epithelial cells

Abstract Background Silica exposure underlies the development of silicosis, one most serious occupational hazards worldwide. We aimed to explore interaction silica-induced epithelial–mesenchymal transition (EMT)-related transcripts with cellular metabolism regulated by p53. Methods knocked out p53 using CRISPR/Cas9 in human bronchial epithelial (HBE) cell line. The transcriptomic and metabolomic analyses integrative omics were conducted microarrays, GC–MS, MetaboAnalyst, respectively. Results Fifty-two mRNAs showed significantly altered expression HBE p53-KO cells post-silica exposure. A total 42 metabolites putatively involved p53-dependent silica-mediated dysfunction. Through integrated data analysis, we obtained five significant metabolic pathways including phenylalanine, glyoxylate, dicarboxylate, linoleic acid metabolism, citrate cycle. metabolite screening, further identified that benzeneacetic acid, a key regulation phenylalanine pathway, attenuated EMT manner. Interestingly, despite extensive p53-related published literature, clinical translation these studies remains unsubstantial. Conclusions Our study offers new insights into molecular mechanisms which respond silica provide fresh perspective direction for future biomarker research potential clinically sustainable translatable role