Manganese (Mn) is required in various human physiological processes. Excessive Mn exposure causes manganism, a progressive neurodegenerative disorder similar to idiopathic Parkinson's disease (IPD). However, the detailed mechanism of Mn-induced neurotoxicity is not yet fully understood. MicroRNAs (miRNAs) play important roles in gene expression regulation, and miRNA expression profile provides additional biological and prognostic information of diseases. In our study, RNA sequencing was performed to profile miRNAs in the SH-SY5Y cells following MnCl2 treatment. Expressions of 73 miRNAs were altered following excessive Mn treatment. Furthermore, has-miR-4306 was identified to target 3'UTR of ATP13A2 (PARK9) directly. Inhibition of has-miR-4306 efficiently restored Mn-induced cytotoxicity. Thus, for the first time, we revealed the miRNA effects of Mn ions to neuron cells, highlighted the involvement of miRNA regulation in neurodegeneration caused by Mn exposure, and provided a potential application of miRNAs in future therapeutic intervention. (C) 2017 Elsevier Inc. All rights reserved.