Mechanism underlying the targeted regulation of the SOD1 3'UTR by the AUF1/Dicer1/miR-155/SOD1 pathway in sodium arsenite-induced liver injury.

Arsenic (As) is a natural hepatotoxicity inducer that is ubiquitous in water, soil, coal, and food. Studies have found that arsenite exposure elicits increased mRNA transcription and decreased protein expression of SOD1 in vivo and in vitro; however, the specific mechanisms remain unclear. Here, we established a model of arsenic-induced chronic liver injury by providing rats with drinking water containing different concentrations of sodium arsenite (NaAsO) and found that NaAsO exposure decreased the mRNA and protein levels of AUF1 and the protein level of SOD1 and elevated the mRNA and protein levels of Dicer1 and miR-155 and the mRNA level of SOD1. Overexpression of AUF1 under NaAsO stress in vitro induced Dicer1 mRNA and protein expression and decreased miR-155 levels, which could be reversed by AUF1 siRNA. In addition, miR-155 overexpression downregulated SOD1 mRNA and protein levels, although this change was inhibited after transfection with an miR-155 inhibitor. Taken together, our findings showed that NaAsO could upregulate Dicer1 mRNA and protein, thereby increasing miR-155 expression by downregulating AUF1 mRNA and protein expression. A dual-luciferase reporter assay indicated that miR-155 decreased the mRNA and protein levels of SOD1 by targeting the SOD1 3'UTR, resulting in liver injury. This study provides an important research basis for further understanding the factors underlying arsenic-induced liver injury to improve the prevention and control strategies for arsenism.