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Updated: Jun 3, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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Transcription factor MAZ activates the transcription of hypomethylated TYMP in ccRCC

Yihan Dong1, Xinyu Liu1, Jiaxin Li1

  • 1School of Medical Technology, Tianjin Medical University, Tianjin, 300203, China.

Functional & Integrative Genomics
|January 11, 2025
PubMed

Insights

Clear cell renal cell carcinoma (ccRCC) involves elevated thymidine phosphorylase (TYMP) expression, regulated by MAZ. TYMP promoter methylation correlates with ccRCC progression and patient survival, offering prognostic potential.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Clear cell renal cell carcinoma (ccRCC) is an aggressive malignancy with high recurrence and metastasis rates.
  • DNA methylation is a key epigenetic mechanism crucial for cancer diagnosis and progression.
  • Understanding gene regulation in ccRCC is vital for developing targeted therapies.

Purpose of the Study:

  • To investigate target genes regulated by MYC-associated zinc finger protein (MAZ) in ccRCC using multi-omics data.
  • To identify the role of thymidine phosphorylase (TYMP) and its regulatory mechanisms in ccRCC.
  • To explore the potential of TYMP promoter methylation as a prognostic biomarker.

Main Methods:

  • Multi-omics data analysis to identify MAZ-regulated genes.
  • Chromatin immunoprecipitation (ChIP) assays to confirm MAZ-TYMP interaction.
  • Bioinformatics analysis and Gene Ontology (GO) enrichment to study gene pathways and interactions.
  • Analysis of TYMP promoter methylation status in relation to clinicopathological data.

Main Results:

  • Thymidine phosphorylase (TYMP) was identified as a gene with significantly elevated expression in ccRCC.
  • MAZ directly binds to the TYMP promoter, and this binding is influenced by promoter methylation status.
  • TYMP promoter methylation correlates with ccRCC clinicopathological stage and overall patient survival.
  • Uridine phosphorylase 1 (UPP1) was found to interact with TYMP and is also activated by MAZ, indicating a coordinated regulatory network in nucleotide metabolism.

Conclusions:

  • The TYMP-UPP1 complex, co-regulated by MAZ, plays a significant role in nucleotide metabolism within ccRCC.
  • TYMP contributes to ccRCC pathophysiology, and its promoter methylation serves as a potential prognostic indicator.
  • These findings provide insights into ccRCC molecular mechanisms and suggest potential therapeutic targets.
Keywords:
CcRCCMAZMethylationNucleotide metabolismTYMP

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