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ZNF652 exerts a tumor suppressor role in lung cancer by transcriptionally downregulating cyclin D3

Chunfeng Xie1, Xu Zhou1, Jinyi Wu1

  • 1Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China.

Cell Death & Disease
|November 5, 2024
PubMed

Insights

Zinc finger protein 652 (ZNF652) acts as a tumor suppressor in lung cancer (LC). Lower ZNF652 levels correlate with poor survival, while its restoration inhibits tumor growth by halting cell cycle progression and inducing senescence.

Area of Science:

  • Molecular Oncology
  • Cancer Biology

Background:

  • Zinc finger protein 652 (ZNF652) dysfunction is linked to various cancers.
  • The specific role of ZNF652 in lung cancer (LC) pathogenesis remains largely undefined.

Purpose of the Study:

  • To investigate the function and mechanism of ZNF652 in lung cancer.
  • To determine if ZNF652 can serve as a prognostic biomarker for LC patients.

Main Methods:

  • Analysis of ZNF652 expression in human LC tissues and cell lines.
  • In vitro studies involving ZNF652 overexpression and knockdown in LC cells.
  • RNA-sequencing (RNA-seq) to identify affected biological pathways.
  • Cell cycle analysis, senescence assays, and apoptosis studies.
  • Mechanistic investigation of ZNF652 binding to the cyclin D3 promoter.
  • In vivo tumor xenograft models.

Main Results:

  • ZNF652 was significantly downregulated in LC tissues and associated with poorer patient survival.
  • ZNF652 overexpression suppressed LC cell viability, proliferation, migration, and invasion.
  • ZNF652 induced G1 phase cell cycle arrest, increased DNA damage, promoted cellular senescence, and enhanced cisplatin-induced apoptosis.
  • ZNF652 directly inhibited cyclin D3 (CCND3) transcription, and CCND3 re-expression rescued ZNF652's effects.
  • ZNF652 overexpression suppressed tumor growth in vivo.

Conclusions:

  • ZNF652 functions as a tumor suppressor in lung cancer.
  • ZNF652 exerts its tumor suppressive effects by inducing cell cycle arrest and senescence through transcriptional downregulation of cyclin D3.
  • ZNF652 holds potential as a prognostic biomarker for lung cancer.

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