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

Mercuric chloride (HgCl₂), 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 HgCl₂-induced neurotoxicity using PC12 cells as a model system. Cells were treated with HgCl₂ 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 HgCl₂-induced neurotoxicity eby downregulating LMO4 and suppressing the Akt/GSK3β/mTOR pathway.

Akt/GSK3β/mTOR; LMO4; Mercury chloride; Neurotoxicity; Oxidative stress; miR-143-3p.