ArticleTranslational oncology2025
PER3 suppresses tumor metastasis of oral squamous cell carcinoma by promoting HIF-1α degradation.
Article in Translational oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Role of the circadian rhythm in squamous cell carcinoma: From molecular mechanism to therapy (Review).Molecular medicine reports · 2026Review
- Impact of Depth of Invasion in Node-Negative Oral Tongue Cancer Treated With Surgery Alone.The Kaohsiung journal of medical sciences · 2026Article
- Circadian clock and cancer.Military Medical Research · 2026Review
- Integrative analysis of fatty acid metabolism and identification ofJournal of thoracic disease · 2025Article
- Postoperative radiotherapy improves long-term survival in HER2-positive metastatic breast cancer: real-world evidence from the latest SEER database.Breast cancer research and treatment · 2025Article
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8 authors.
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Abstract
The low expression of period circadian regulator 3 (PER3) in head and neck squamous cell carcinoma is closely correlated with tumor size and invasion depth. Hypoxia-inducible factor 1 subunit alpha (HIF-1α) regulates epithelial-mesenchymal transition (EMT) transcription factors, activates EMT, and promotes tumor metastasis. Here, we investigated the role and molecular mechanism of PER3 in regulating HIF-1α and metastasis in oral squamous cell carcinoma (OSCC) by using bioinformatics analyses and in vitro and in vivo experiments. PER3 expression was decreased in OSCC, and PER3 expression was significantly negatively correlated with T stage, N stage, clinical classification, and survival time. PER3 overexpression inhibited, while PER3 knockdown prompted EMT and metastasis of OSCC cells. HIF-1α reversed the effects of alterations in PER3 expression on OSCC metastasis. Mechanistically, PER3 bound to HIF-1α via the Per-ARNT-Sim 1 domain and promoted its ubiquitination degradation. Hypermethylation at CpG site cg12258811 of PER3 promoter inhibited PER3 expression and prognosis of OSCC. Decitabine combined with LW6 upregulated PER3, downregulated HIF-1α, and inhibited lymph node metastasis of OSCC in nude mice. Our findings reveal the role and mechanism of HIF-1α regulation by PER3 and support the potential clinical application of targeting PER3 in treating OSCC metastasis.
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