Integrative transcriptome analysis of human cells treated with silver nanoparticles reveals a distinct cellular response and the importance of inorganic elements detoxification pathways

The field of Nanotechnology has taken a great leap in recent decades, with several products currently researched in the industrial sector and even available in the market bringing nanostructured components. The pharmaceutical industry has explored this type of structure as targeted drug delivery, especially against cancer. Integrative transcriptome analysis (ITA) is considered a promising technique for understanding biological events by analyzing several transcriptomes deposited in public databases. This research recovered seven transcriptomes' studies of human cells treated with silver nanoparticles without association or conjugation with any other substance or material for the performance of ITA. This analysis consists of a bipartite network for determining shared differentially expressed genes (DEGs) between different datasets from human cells treated with silver nanoparticles (AgNPs) at both early (4 or 6 h) and late treatment time (24 h). Most of the few upregulated DEGs shared by five or more datasets belong to biological pathways related to mineral absorption, suggesting that these processes were upregulated in AgNPs-treated cells. In addition, Ferroptosis, protein processing in the endoplasmic reticulum, and mitogen-activated protein kinase (MAPK) signaling pathway were also upregulated. Thus, the ITA of human cells treated with AgNPs indicates that the expression profile induced by these nanoparticles is specific to each cell type. However, they share inorganic compounds and oxidative stress responses genes, triggering apoptosis. This work reinforces the need for the biological characterization of cellular response to silver nanoparticles for application in humans, thus ensuring the safety and optimization of the desired results.