miR-143-3p mediates mercury chloride-induced neurotoxicity by targeting LMO4 and the Akt/GSK3β/mTOR pathway in vitro.

Mercuric chloride (HgCl(2)), a common environmental neurotoxin, induces neuronal injury through incompletely characterized mechanisms. Recent findings suggest a regulatory role for microRNAs (miRNAs) in mercury-induced neurotoxicity, with miR-143-3p significantly enriched in the brain and implicated in neuronal viability. This study investigated the functional role and underlying mechanisms of miR-143-3p in HgCl(2)-induced neurotoxicity using PC12 cells as a model system. Cells were treated with HgCl(2) for 48 h, followed by evaluation of cell viability and apoptosis via MTT assay and flow cytometry, respectively. Neuronal morphology was assessed using inverted phase-contrast microscopy, while reactive oxygen species (ROS) levels were quantified using DCFH-DA staining. The expression levels of miR-143-3p and its downstream targets were determined by RT-qPCR, and protein expression was analyzed through western blotting. A luciferase reporter assay was employed to confirm the interaction between miR-143-3p and LMO4. Results revealed that silencing miR-143-3p alleviated HgCl₂-induced neurotoxicity in PC12 cells. Mechanistically, miR-143-3p was found to directly bind the 3' untranslated region (3'UTR) of LMO4. Overexpression of LMO4 conferred protection against HgCl₂-induced neuronal damage. Further analysis showed that miR-143-3p suppresses the Akt/GSK3β/mTOR signaling cascade by targeting LMO4. Either silencing LMO4 or pharmacologically inhibiting Akt diminished the neuroprotective effects observed upon miR-143-3p knockdown. These findings suggest that miR-143-3p exacerbates HgCl(2)-induced neurotoxicity eby downregulating LMO4 and suppressing the Akt/GSK3β/mTOR pathway.