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Background <p>The extracellular matrix (ECM) plays a pivotal role in lung adenocarcinoma (LUAD) progression and chemoresistance, yet its regulatory mechanisms remain incompletely understood. Here, we identify ZNF514 as a novel tumour suppressor that critically governs ECM remodelling.</p> Methods <p>To elucidate the role of ZNF514 in LUAD, we employed a multi-platform approach integrating LUAD organoids, tumour specimens, xenograft mouse models, and cancer cell lines. Transcriptomic profiling was performed to assess ZNF514 expression and its clinical prognostic relevance. Mechanistically, chromatin immunoprecipitation (ChIP) assay, dual-luciferase reporter assay and pathway enrichment analyses identified ZNF514 as a transcriptional repressor of collagen-encoding genes.</p> Results <p>Analyses of LUAD clinical tissues, patient-derived organoids, and The Cancer Genome Atlas (TCGA) datasets revealed a significant downregulation of ZNF514, which correlated with poor prognosis. Functionally, ZNF514 overexpression suppressed organoid formation, subcutaneous tumour growth, and cellular migration and invasion, while enhancing cisplatin (DDP) sensitivity. Mechanistically, RNA sequencing, ChIP assay and dual-luciferase reporter assays identified COL1A1 as a direct transcriptional target of ZNF514. ZNF514 directly binds to the COL1A1 promoter and represses its transcription, thereby contributing, at least in part, to altered extracellular matrix (ECM) remodelling and attenuation of COL1A1-associated epithelial–mesenchymal transition (EMT) in LUAD models.</p> Conclusions <p>Together, these findings identify ZNF514 as a tumour-suppressive transcription factor that inhibits LUAD proliferation, invasion, and migration and enhances cisplatin sensitivity, at least in part, through transcriptional repression of COL1A1 and modulation of ECM remodelling.</p>

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Novel transcription factor zinc finger 514 suppresses lung adenocarcinoma progression and enhances cisplatin sensitivity via transcriptional repression of COL1A1

  • 期刊论文

  • 发表日期：

    2026年4月9日

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  • Shengnan Sun,
  • Guoyuan Ma,
  • Lin Cheng,
  • Huiping Zhang,
  • Gonglin Fan,
  • Lei Wu,
  • Xiangwei Zhang,
  • Fuyuan Xue,
  • Tingting Fu,
  • Xingzhao Ji,
  • Qiang Wan,
  • Yi Liu

摘要

Background

The extracellular matrix (ECM) plays a pivotal role in lung adenocarcinoma (LUAD) progression and chemoresistance, yet its regulatory mechanisms remain incompletely understood. Here, we identify ZNF514 as a novel tumour suppressor that critically governs ECM remodelling.

Methods

To elucidate the role of ZNF514 in LUAD, we employed a multi-platform approach integrating LUAD organoids, tumour specimens, xenograft mouse models, and cancer cell lines. Transcriptomic profiling was performed to assess ZNF514 expression and its clinical prognostic relevance. Mechanistically, chromatin immunoprecipitation (ChIP) assay, dual-luciferase reporter assay and pathway enrichment analyses identified ZNF514 as a transcriptional repressor of collagen-encoding genes.

Results

Analyses of LUAD clinical tissues, patient-derived organoids, and The Cancer Genome Atlas (TCGA) datasets revealed a significant downregulation of ZNF514, which correlated with poor prognosis. Functionally, ZNF514 overexpression suppressed organoid formation, subcutaneous tumour growth, and cellular migration and invasion, while enhancing cisplatin (DDP) sensitivity. Mechanistically, RNA sequencing, ChIP assay and dual-luciferase reporter assays identified COL1A1 as a direct transcriptional target of ZNF514. ZNF514 directly binds to the COL1A1 promoter and represses its transcription, thereby contributing, at least in part, to altered extracellular matrix (ECM) remodelling and attenuation of COL1A1-associated epithelial–mesenchymal transition (EMT) in LUAD models.

Conclusions

Together, these findings identify ZNF514 as a tumour-suppressive transcription factor that inhibits LUAD proliferation, invasion, and migration and enhances cisplatin sensitivity, at least in part, through transcriptional repression of COL1A1 and modulation of ECM remodelling.