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<p>Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is associated with a poorer prognosis compared to its HPV-positive counterpart; however, the underlying regulatory molecular mechanisms driving its progression remain poorly understood. In this study, we identify BTB Domain and CNC Homolog 1 (BACH1) as a critical oncogenic regulator that is upregulated in HPV-negative HNSCC. We demonstrate that BACH1 promotes tumor progression by enhancing the proliferation and inhibiting apoptosis of cancer cells. Mechanistically, BACH1 is associated with the SWI/SNF chromatin remodeling complex and transcriptionally activates downstream target genes, including <i>IL1B</i>, thereby inducing a transcriptional reprogramming that promotes proliferation and resists apoptosis. Notably, BACH1-driven upregulation of interleukin-1β (IL-1β) establishes a positive feedback loop that sustains oncogenic signaling. Pharmacological disruption of this axis using the IL-1 receptor antagonist Anakinra significantly attenuates tumor growth in vitro<i> and </i>in vivo. Clinically, co-upregulation of BACH1, BRG1, and IL-1β is correlated with reduced overall survival in patients with HPV-negative HNSCC. Collectively, our findings characterize the BACH1–IL-1β signaling axis as a prognostic biomarker and highlight IL-1R blockade as a promising therapeutic strategy for the treatment of HPV-negative HNSCC.</p>

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A positive feedback loop between BACH1 and IL-1β promotes the progression of HPV-negative head and neck squamous cell carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月25日

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  • Zishanbai Zhang,
  • Miao Wang,
  • Wenjuan Wang,
  • Minghui Zhao,
  • Yiming Ding,
  • Tingyao Ma,
  • Zhaohan Zhang,
  • Xilin Wang,
  • Yuchen Xiang,
  • Yaning Wang,
  • Wenying Zhong,
  • Zicheng Wu,
  • Yiran Meng,
  • Xiaohong Chen,
  • Lin Shan

摘要

Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is associated with a poorer prognosis compared to its HPV-positive counterpart; however, the underlying regulatory molecular mechanisms driving its progression remain poorly understood. In this study, we identify BTB Domain and CNC Homolog 1 (BACH1) as a critical oncogenic regulator that is upregulated in HPV-negative HNSCC. We demonstrate that BACH1 promotes tumor progression by enhancing the proliferation and inhibiting apoptosis of cancer cells. Mechanistically, BACH1 is associated with the SWI/SNF chromatin remodeling complex and transcriptionally activates downstream target genes, including IL1B, thereby inducing a transcriptional reprogramming that promotes proliferation and resists apoptosis. Notably, BACH1-driven upregulation of interleukin-1β (IL-1β) establishes a positive feedback loop that sustains oncogenic signaling. Pharmacological disruption of this axis using the IL-1 receptor antagonist Anakinra significantly attenuates tumor growth in vitro and in vivo. Clinically, co-upregulation of BACH1, BRG1, and IL-1β is correlated with reduced overall survival in patients with HPV-negative HNSCC. Collectively, our findings characterize the BACH1–IL-1β signaling axis as a prognostic biomarker and highlight IL-1R blockade as a promising therapeutic strategy for the treatment of HPV-negative HNSCC.