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KRAB-containing zinc finger protein ZNF496 inhibits breast cancer cell proliferation by selectively repressing ERα

Jinlong Wang1, Xiuyuan Zhang2, Jiming Ling3

  • 1School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province 261053, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China; Department of Pathology, The 422th Hospital of PLA, Zhanjiang, Guangdong Province 524000, China.

Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms
|July 18, 2018
PubMed

Insights

ZNF496, a KRAB-containing zinc finger protein (KZNF), acts as a corepressor for estrogen receptor alpha (ERα). It inhibits ERα-positive breast cancer cell growth and its downregulation correlates with poor patient survival.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • KRAB-containing zinc finger proteins (KZFPs) are the largest family of human transcriptional regulators, crucial in development and cancer.
  • The specific functions and mechanisms of most KZFPs are not well understood.
  • Estrogen receptor alpha (ERα) is a key regulator in normal development and a driver of ERα-positive breast cancer.

Purpose of the Study:

  • To investigate the function and mechanism of the KRAB-containing zinc finger protein ZNF496.
  • To determine ZNF496's role in estrogen receptor alpha (ERα) activity and ERα-positive breast cancer.

Main Methods:

  • Co-immunoprecipitation assays to identify protein interactions.
  • Chromatin immunoprecipitation (ChIP) to assess DNA binding.
  • Quantitative real-time PCR (qRT-PCR) to analyze gene expression.
  • Analysis of clinical breast cancer patient data.

Main Results:

  • ZNF496 directly interacts with the DNA binding domain of ERα via its C2H2 domain.
  • This interaction reduces ERα binding to chromatin, represses ERα transactivation, and selectively suppresses ERα target genes.
  • ZNF496 downregulation was observed in ERα-positive breast cancer tissues and associated with poorer recurrence-free survival.

Conclusions:

  • ZNF496 is a novel ERα-binding protein and a target gene-specific ERα corepressor.
  • ZNF496 inhibits the growth of ERα-positive breast cancer cells.
  • Downregulation of ZNF496 is linked to adverse outcomes in breast cancer patients.
Keywords:
Breast cancerCorepressorEstrogen receptor αKZNFTarget gene

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