Session: Bioinorganic Chemistry:

Gold nanoparticles (AuNPs) are promising nanomaterials in biomedicine, and their presence in consumer products is growing over time, raising concerns about the intersection of NPs with living systems. The new vision for the safety assessment of chemicals/NPs is based on the mechanistic understanding of the biological responses triggered by them, including the use of omics-based and systems biology approaches. MicroRNAs (miRNAs), short non-coding RNAs that mediate gene expression repression, have emerged as key regulators of biological pathways, and play pivotal roles in cellular responses to environmental chemicals. Herein, we report the first study focused on the in vitro long-term effects of a low dose of AuNPs with varying shapes and surface coatings in the global miRNA expression profile of human fibroblasts after chronic and acute (non-chronic) exposures. Our results show that the exposure condition and surface chemistry of the AuNPs do have a significant impact on the modulation of miRNA levels. At the systems-level perspective, the biological response for a long-term low dose is distinctly different: the non-chronic exposure to AuNPs led to significant perturbation in miRNA networks enriched for target genes involved in cell proliferation pathways, with cells under this exposure condition potentially suppressing proliferative signaling pathways, possibly an attempt to restore cell homeostasis disrupted after the treatment with AuNPs, while changes in miRNA co-expression networks enriched for target genes related to activation of proliferative and suppression of apoptotic pathways were observed in cells chronically exposed to one specific type of AuNPs. In this case, miRNA dysregulation might be contributing to enforce a new cell phenotype during stress. Collectively, our data suggest that miRNAs play critical roles in the cellular responses to the stress provoked by AuNP stimuli.

Catherine Murphy

Appearances