2. Academic Validation
  3. Peroxiredoxin 1 regulates crosstalk between pyroptosis and autophagy in oral squamous cell carcinoma leading to a potential pro-survival

Peroxiredoxin 1 regulates crosstalk between pyroptosis and autophagy in oral squamous cell carcinoma leading to a potential pro-survival

  • Cell Death Discov. 2023 Nov 25;9(1):425. doi: 10.1038/s41420-023-01720-7.
Meilin Ye # 1 2,  Ting Liu # 1 2,  Shanshan Liu 1 2,  Rong Tang 1 2,  Hongrui Liu 1 2,  Fan Zhang 3,  Shenglei Luo 4,  Minqi Li 1 2
Affiliations

Affiliations

  • 1 Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China.
  • 2 Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China.
  • 3 Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China. zhfan@sdu.edu.cn.
  • 4 Department of Oral and Maxillofacial Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. luodentist@163.com.
  • # Contributed equally.
PMID: 38007535 DOI: 10.1038/s41420-023-01720-7
Abstract

Peroxiredoxin 1 (Prdx1), a vital antioxidant Enzyme, has been proven to play an important role in the occurrence and development of cancers, but its effects on oral squamous cell carcinoma (OSCC) remain unclear. Here, we performed bioinformatics analysis and immunohistochemical (IHC) staining to confirm that Prdx1 was higher in OSCC tissues than in normal tissues. Consistently, RT-PCR and Western blot showed elevated Prdx1 expression in OSCC cell lines compared to human oral keratinocytes (HOK), which could be knockdown by small interfering RNA (siRNA) and Lentiviral vector delivery of short hairpin RNA (shRNA). Prdx1 silencing significantly blocked OSCC cell proliferation and metastasis, as evidenced by the CCK8, colony formation, in vivo tumorigenesis experiment, wound healing, transwell assays, and changes in migration-related factors. siPrdx1 transfection increased intracellular Reactive Oxygen Species (ROS) levels and provoked Pyroptosis, proved by the upregulation of pyroptotic factors and LDH release. Prdx1 silencing ROS-independently blocked Autophagy. Mature autophagosome failed to form in the siPrdx1 group. Up-regulated Autophagy limited Pyroptosis triggered by Prdx1 deficiency, and down-regulated Pyroptosis partly reversed siPrdx1-induced Autophagy defect. Collectively, Prdx1 regulated Pyroptosis in a ROS-dependent way and modulated Autophagy in a ROS-independent way, involving the crosstalk between Pyroptosis and Autophagy.

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