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ZNF331 Represses the Proliferation of Head and Neck Squamous Cell Carcinoma via Co-Repressor TRIM28

Ju Li1,2, Hao Cheng3, Yong Zhao3

  • 1Department of Stomatology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.

Oral Diseases
|November 26, 2024
PubMed
Abstract

Insights

Zinc Finger Protein 331 (ZNF331) suppresses Head and Neck Squamous Cell Carcinoma (HNSCC) growth. Its inactivation via DNA methylation contributes to HNSCC, suggesting ZNF331 restoration as a potential therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Head and Neck Squamous Cell Carcinoma (HNSCC) is a complex malignancy.
  • The role of Zinc Finger Protein 331 (ZNF331), a transcriptional repressor, in HNSCC remains largely unexplored.

Purpose of the Study:

  • To investigate the regulatory role of ZNF331 in HNSCC.
  • To elucidate the mechanisms underlying ZNF331 dysregulation and its impact on tumor progression.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA)-HNSC data.
  • In vitro and in vivo experiments assessing ZNF331's effects on cell proliferation, cell cycle, and oncogene expression.
  • Investigation of epigenetic modifications, including promoter methylation and DNA methyltransferase (DNMT) activity.

Main Results:

  • Higher ZNF331 expression correlates with improved progression-free survival in HNSCC patients.
  • ZNF331 overexpression inhibits HNSCC proliferation and induces G2/M arrest, while knockdown promotes oncogenesis.
  • ZNF331 downregulates oncogenes (DDX5, EIF5A, SET) and requires TRIM28 for its tumor-suppressive function.
  • DNMT3B-mediated promoter hypermethylation suppresses ZNF331 expression; DNMT3B knockdown restores it.

Conclusions:

  • ZNF331 functions as a tumor suppressor in HNSCC.
  • DNMT3B-mediated hypermethylation inactivates ZNF331, contributing to HNSCC development.
  • Restoring ZNF331 expression via epigenetic therapy presents a potential treatment strategy for HNSCC.
Keywords:
TRIM28ZNF331head and neck squamous cell carcinomapromoter methylation

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