Modulation of miRNA-155 alters manganese nanoparticle-induced inflammatory responseElectronic supplementary information (ESI) available: Optimization of transfection, potential toxicity of the miR-155 mimic, and cell viability following miR-155 restoration along with the complete list of miRNAs that were differentially expressed based on the next generation sequencing data. See DOI: 10.1039/c6tx00208k

• Main Authors: Grogg, Matthew W, Braydich-Stolle, Laura K, Maurer-Gardner, Elizabeth I, Hill, Natasha T, Sakaram, Suraj, Kadakia, Madhavi P, Hussain, Saber M
• Format: Journal Article
• Language: English
• Published: 24.10.2016
• ISSN: 2045-452X; 2045-4538
• DOI: 10.1039/c6tx00208k

Regulation of gene expression by non-coding RNAs, such as microRNAs (miRNAs), is increasingly being examined in a variety of disciplines. Here we evaluated changes in miRNA expression following metallic nanoparticle (NP) exposure in a mouse neuronal co-culture model. Exposure to manganese (Mn) NPs resulted in oxidative stress, inflammation, and toxicity. Next-generation sequencing (NGS) following an 8 h exposure to Mn NPs (low and high doses) revealed several miRNA candidates that modulate NP induced responses. The lead candidate identified was miR-155, which showed a dose dependent decrease in expression upon Mn exposure. Introduction of a miR-155 mimic into the co-culture to restore miR-155 expression completely abrogated the Mn NP-induced gene and protein expression of inflammatory markers TNF-α and IL-6. Taken together, this study is the first report where global NP-induced miRNA expression changes were used to identify and then modulate negative impacts of metallic NP exposure in a neuronal model. These findings demonstrate that unique miRNA expression profiles provide novel targets for manipulating gene and protein expression, and therefore provide the potential of modifying cellular responses to NP exposure. This novel study identified miRNA targets following MnNP exposure, which were modulated to alter cellular responses.