Abstract:

Objective To investigate the regulatory mechanism of miRNA in metallic cadmium-induced acute liver injury，screen key molecules of miRNAs associated with cadmium induced liver injury. Methods Male C57BL/6 mice were randomly divided into a control group and a cadmium-exposed group. The exposed group received intraperitoneal injections of 2 mg/kg cadmium chloride solution，while the control group was administered normal saline. The serum and liver tissues were collected post-exposure to evaluate liver injury severity and measure the expression levels of miR345-5p and its target gene GSTM2. L02 cells were treated with metallic cadmium to assess changes in cell viability and the expression of miR345-5p and GSTM2. The dual-luciferase reporter system was employed to validate miR345-5p's regulatory effect on GSTM2. Results The metallic cadmium exposure induced acute inflammatory responses in mouse livers，with miR345-5p expression increasing by 6.85-fold and GSTM2 expression decreasing by 0.64-fold. In L02 cells，miR345-5p and GSTM2 exhibited a dose-response relationship to cadmium exposure. Transfection with miR345-5p mimic reduced the mRNA expression of GSTM2 and decreased cell viability by 72.38% in cadmium-treated cells. The dual-luciferase assay confirmed that miR345-5p mimic significantly reduced fluorescence intensity in the wild-type group but not in the mutant group. Conclusion The miR345-5p exacerbates metallic cadmium-induced acute liver injury by downregulating GSTM2 expression.

Key words: MicroRNA, Acute Liver Injury, Cadmium, miR-345-5p, Glutathione S-transferase, Phase Ⅱdetoxification enzyme