Modulation of miRNA-155 alters manganese nanoparticle-induced inflammatory response

Abstract

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.