METTL3 mediated bisphenol A(BPA)-induced placental toxicity through regulating miR-146a to promote ferroptosis
Objective Based on the differentially expressed miRNAs of bisphenol A(BPA)-induced toxicity through Gene Expression Database(GEO),the functional pathway of differentially expressed genes was investigated.At the same time,the mechanism of METTL3-mediated BPA-induced placental toxicity was explored.Methods GEO online analysis tool(GEO2R)was used to screen the differentially expressed genes,and the pathway enrichment was analyzed after BPA exposure.miRNAcode and Targetscan predictive software were used to identify the target genes of differentially expressed miRNA.The JEG3 cells exposed to BPA was established at different concentrations,and the cytotoxicity of BPA was detected by MTT.The concentrations of BPA were selected for the mechanism of BPA-induced placental toxicity.GPX4,the key protein of ferrop-tosis,was analyzed by immunofluorescence analysis.The expression level of METTL3 protein was detected by Western blot-ting.Results miR-146a was differentially expressed in the placenta of pregnant women exposed to BPA by GEO analysis,and significant enrichment items were obtained by GO function analysis,including cell death pattern,metabolism,and information communication between cells.miRNAcode and Targetscan analysis showed the co-network of miR-146a,which included 20 target genes.SLC7A11,a target gene of miR-146a,was not only the target gene of miR-146a but also a key protein in ferrop-tosis.miR-146a expression is regulated by the m6A methyltransferase METTL3.With the increase of BPA concentration,the expression of METTL3 also showed an upward trend.Conclusion BPA exposure upregulated the expression of miR-146a by regulating METTL3,and miR-146a promotes ferroptosis by targeting its target gene SLC7A11,thereby mediating the placental toxicity induced by BPA.
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