miR-129-5p regulates HMGB1/RAGE axis to inhibit pyroptosis and ameliorate cervical epithelial cell deterioration

Cervical cancer is a serious gynecological malignancy, and the specific mechanisms of miR-129-5p remain unclear. This study aims to investigate the mechanism by which miR-129-5p regulates the high mobility group box 1 (HMGB1/receptor for advanced glycation end-products (RAGE) axis to inhibit pyroptosis and ameliorate cervical epithelial cell deterioration. Using RT-qPCR and Western blotting, we detected significantly downregulated miR-129-5p and upregulated HMGB1 in cervical cancer cells. To establish a deterioration model, we stimulated cervical epithelial cells with lipopolysaccharide (LPS). Further results revealed that miR-129-5p overexpression markedly reduced HMGB1 expression, suppressed RAGE activation, and decreased pyroptosis executer GSDMD-N production. Additionally, we conducted miR-129-5p overexpression and knockdown experiments to verify its regulatory effects on the HMGB1/RAGE axis and downstream pathways. Caspase-1 activity assays confirmed reduced pyroptosis upon miR-129-5p overexpression. Cell viability and proliferation were assessed using EdU incorporation assays and colony formation experiments. Our data demonstrated significant downregulation of miR-129-5p in cervical cancer cells. Overexpression of miR-129-5p substantially reduced HMGB1 expression and inhibited RAGE activation, thereby decreasing production of the pyroptosis executer GSDMD-N. LPS stimulation potently activated the HMGB1/RAGE axis and induced pyroptosis, while miR-129-5p overexpression inhibited these processes and ameliorated in vitro cervical epithelial cell deterioration. Cells overexpressing miR-129-5p exhibited attenuated caspase-1 activity with enhanced survival and proliferation following LPS treatment. Collectively, these in vitro findings indicate that miR-129-5p suppresses HMGB1/RAGE-mediated pyroptosis and cellular deterioration and also provide new mechanistic insights for cervical cancer therapeutics.