Aberrant expression of miRNA‐192‐5p contributes to N,N‐dimethylformamide‐induced hepatic apoptosis.

Excessive exposure to N,N‐dimethylformamide (DMF) can lead to occupational liver poisoning in workers; however, the underlying mechanism is not fully clarified. The importance of microRNAs (miRNAs) in chemical‐induced hepatotoxicity has been demonstrated. To determine whether miRNAs are also involved in DMF‐induced hepatotoxicity, we systematically analyzed the miRNA expression profiles in DMF‐treated (75 and 150 mm) HL‐7702 liver cells and controls by high‐throughput sequencing. Among the altered miRNAs, miR‐192‐5p was the most significantly upregulated in HL‐7702 cells after DMF exposure and was involved in DMF‐mediated cell apoptosis. By contrast, suppression of miR‐192‐5p in HL‐7702 cells attenuated the apoptosis induced by DMF. Furthermore, the anti‐apoptotic gene (NIN1/RPN12 binding protein 1 homolog [NOB1]) was predicted to be a potential miR‐192‐5p target according to bioinformatics analysis. The direct interaction between miR‐192‐5p and NOB1 was confirmed by the dual‐luciferase activity assay in HEK293FT cells. Overexpression of miR‐192‐5p efficiently reduced NOB1 mRNA and protein expression in HL‐7702 cells. Alteration in NOB1 expression influenced DMF‐induced hepatotoxicity by affecting hepatic apoptosis. In addition, the inverse correlation between miR‐192‐5p expression levels and NOB1 expression was further confirmed in DMF‐exposed mouse liver tissue samples. These observations demonstrated that promotion of apoptosis from the suppression of NOB1 by miR‐192‐5p overexpression was responsible for the DMF‐induced hepatotoxicity. This work provides the molecular mechanism at the miRNA level for hepatic apoptosis induced by DMF. DMF can lead to occupational liver poisoning. DMF exposure can result in the upregulation of miR‐192‐5p expression in HL‐7702 cells and liver tissue of ICR mice. The anti‐apoptotic gene NOB1 is the direct target of miR‐192‐5p. Our observations demonstrated that miR‐192‐5p was involved in DMF‐induced hepatocyte apoptosis by inhibiting the expression of NOB1. This work provides the molecular mechanism at the miRNA level for hepatic apoptosis induced by DMF. [ABSTRACT FROM AUTHOR]