Citation:

Thai, S., C. Jones, B. Robinette, H. Ren, B. Vallanat, A. Fisher, AND K. Kitchin. Effects of Silver Nanoparticles and Silver Nitrate on mRNA and microRNA Expression in Human Hepatocellular Carcinoma Cells (HepG2). Journal of Nanoscience and Nanotechnology. American Scientific Publishers , VALENCIA, CA, 21(11):5414-5428, (2021). https://doi.org/10.1166/jnn.2021.19481

Impact/Purpose:

The silver nanoparticles (AgNPs) have extremely large relative surface area to volume ratio, increasing their contact with bacterial, fungi, and viruses, vastly improving its biocidal effectiveness. AgNPs have been among the most commonly used nanomaterials in our health care system for many years. Recently, AgNPs have become of intense interest in biomedical applications because of their antibacterial, antifungal, antiviral, and anti-inflammatory activity. Because of their wide spectrum biocidal nature, silver nanoparticles have been added to a variety of textiles, home goods, food packaging materials, food supplements, household appliances, cosmetics, water disinfectants and medical devices. Nanoparticles (NPs) can be more toxic to human health when compared to their bulk counter parts. It is normally thought that the activity of particles is proportional to their surface area and thus the toxicities are inversely proportional to the size of the NPs. However due to their multiple physiochemical properties in different biological systems, unpredictable health outcomes may be present in different systems. There are many reports on AgNPs causing tissue/organ toxicity in rats. This study is to explore the signaling pathways altered by nano silver treatments in Hep G2 cells (human hepatocellular carcinoma cells) in comparison to silver nitrate treated cells. Both RNA and microRNA profiling were analyzed in this study. The results provided insight into the effects of nano silver on the signaling pathways, and may shed light on the long term toxicity nano silver may cause in vivo.

Description:

In order to understand toxicity of nano silver, human hepatocellular carcinoma (HepG2) cells were treated either with silver nitrate (AgNO¿) or with nano silver capped with glutathione (Ag-S) at various concentration. Differentially expressed genelists for mRNA and microRNA were obtained through Illumina RNA sequencing and DEseq data analyses. Both treatments showed non-linear dose response relationships for mRNA and microRNA. Gene expression analysis showed signaling pathways common to both nano Ag-S and AgNO¿, such as cell cycle regulation, DNA damage response and cancer related pathways. But, nano Ag-S caused signaling pathway changes that were not altered by AgNO¿ such as NRF2-mediated oxidative stress response inflammation, cell membrane signaling, and cell proliferation. Nano Ag-S also affected p53 signaling, survival, apoptosis, tissue repair, lipid synthesis, angiogenesis, liver fibrosis and tumor development. Several of the pathways affected by nano Ag-S are hypothesized as major contributors to nanotoxicity. MicroRNA target filter analysis revealed additional affected pathways that were not reflected in the mRNA expression response alone, including DNA damage signaling, genomic stability, ROS, cell cycle, ubiquitination, DNA methylation, cell proliferation and fibrosis for AgNO¿; and cell cycle regulation, P53 signaling, cell proliferation, survival, apoptosis, tissue repair and so on for nano Ag-S. These pathways may be mediated by microRNA repression of protein translation.Our study clearly showed that the addition of microRNA profiling increased the numbers of signaling pathways discovered that affected by the treatments on HepG2 cells and gave US a better picture of the effects of these reagents in the cells.

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