Articles
Vol. 69 No. 4 (2025)
https://doi.org/10.4081/ejh.2025.4238

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

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Published: 23 September 2025
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Data Availability Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request

miR-129-5p, HMGB1/RAGE axis, pyroptosis, cervical cancer, LPS

Authors

Huafang Wang
First Department of Oncology Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Dilidaer Sidike
First Department of Oncology Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Pan Liu
First Department of Oncology Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Longge Suo
First Department of Oncology Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Huerxidan Niyazi
wanghuafang1215@126.com
First Department of Oncology Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

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.

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Supporting Agencies

Provincial-Ministry Joint Establishment of State Key Laboratory of Causes and Prevention of High Morbidity in Central Asia

How to Cite



1.
Wang H, Sidike D, Liu P, Suo L, Niyazi H. miR-129-5p regulates HMGB1/RAGE axis to inhibit pyroptosis and ameliorate cervical epithelial cell deterioration. Eur J Histochem [Internet]. 2025 Sep. 23 [cited 2025 Dec. 28];69(4). Available from: https://www.ejh.it/ejh/article/view/4238
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