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Background <p>Profilin-2 (PFN2) is implicated in cancer metastasis, yet its significance in oral squamous cell carcinoma (OSCC) is unclear.</p> Methods <p>We quantified PFN2 mRNA and protein in 236 OSCC tumours using qRT-PCR and immunohistochemistry, correlating findings with clinicopathology and survival. Gain- and loss-of-function studies were performed in OSCC cell lines and xenograft mice. RNA sequencing with gene-set enrichment, subcellular fractionation, and immunofluorescence delineated PFN2-dependent pathways. Sensitivity to the histone deacetylase (HDAC) inhibitor SAHA was assessed in vitro.</p> Results <p>High PFN2 expression correlated with lymph-node metastasis, stage IV disease, and poorer overall and disease-free survival (<i>p</i> &lt; 0.01). PFN2 increased proliferation, invasion, and epithelial–mesenchymal transition (EMT) in vitro, and accelerated primary tumour growth plus cervical/lung metastasis in vivo; knockout produced opposite effects. Transcriptomics revealed enrichment of EMT, E2F, G2/M, and hypoxia signatures, with a 44% overlap with HDAC1 targets. PFN2 shifted HDAC1 to the cytoplasm and downregulated NuRD partners MBD3/MTA1 without altering total HDAC1. PFN2-driven EMT was independent of β-catenin nuclear entry. PFN2 overexpression sensitized cells to SAHA, enhancing G2/M arrest, apoptosis, and invasion blockade.</p> Conclusions <p>PFN2 is an oncogenic driver that promotes OSCC progression through HDAC1-dependent transcriptional reprogramming. PFN2 may serve as a prognostic biomarker and predictor of response to HDAC-targeted therapy.</p>

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Profilin-2 promotes tumour aggressiveness in oral squamous cell carcinoma via HDAC1 modulation: implications for EMT and targeted therapy

  • 期刊论文

  • 发表日期：

    2025年11月7日

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  • Li-Han Lin,
  • Kuo-Wei Chang,
  • Hui-Wen Cheng,
  • Chung-Ji Liu

摘要

Background

Profilin-2 (PFN2) is implicated in cancer metastasis, yet its significance in oral squamous cell carcinoma (OSCC) is unclear.

Methods

We quantified PFN2 mRNA and protein in 236 OSCC tumours using qRT-PCR and immunohistochemistry, correlating findings with clinicopathology and survival. Gain- and loss-of-function studies were performed in OSCC cell lines and xenograft mice. RNA sequencing with gene-set enrichment, subcellular fractionation, and immunofluorescence delineated PFN2-dependent pathways. Sensitivity to the histone deacetylase (HDAC) inhibitor SAHA was assessed in vitro.

Results

High PFN2 expression correlated with lymph-node metastasis, stage IV disease, and poorer overall and disease-free survival (p < 0.01). PFN2 increased proliferation, invasion, and epithelial–mesenchymal transition (EMT) in vitro, and accelerated primary tumour growth plus cervical/lung metastasis in vivo; knockout produced opposite effects. Transcriptomics revealed enrichment of EMT, E2F, G2/M, and hypoxia signatures, with a 44% overlap with HDAC1 targets. PFN2 shifted HDAC1 to the cytoplasm and downregulated NuRD partners MBD3/MTA1 without altering total HDAC1. PFN2-driven EMT was independent of β-catenin nuclear entry. PFN2 overexpression sensitized cells to SAHA, enhancing G2/M arrest, apoptosis, and invasion blockade.

Conclusions

PFN2 is an oncogenic driver that promotes OSCC progression through HDAC1-dependent transcriptional reprogramming. PFN2 may serve as a prognostic biomarker and predictor of response to HDAC-targeted therapy.