Global Decrease of Histone H3K27 Acetylation in ZEB1-Induced Epithelial to Mesenchymal Transition in Lung Cancer...

Area of Science:

• Molecular Biology
• Cancer Research
• Epigenetics

Background:

• The epithelial to mesenchymal transition (EMT) is crucial for cancer cell invasion and metastasis.
• ZEB1 is a key transcription factor that represses epithelial genes in lung cancer.

Purpose of the Study:

• To investigate the mechanism by which ZEB1 suppresses epithelial genes in non-small cell lung cancer.
• To explore the role of epigenetic modifications in ZEB1-mediated gene regulation and cancer metastasis.

Main Methods:

• Chromatin immunoprecipitation (ChIP) to identify ZEB1 binding sites.
• Western blot and immunocytochemistry to assess histone acetylation levels.
• Analysis of ZEB1 expression and H3K27 acetylation in lung cancer tissues.

Main Results:

• ZEB1 directly downregulates EpCAM, ESRP1, ST14, and RAB25 in H358 lung cancer cells.
• ZEB1 induction led to decreased H3K9 and H3K27 acetylation at target gene binding sites.
• H3K27 acetylation was lower in ZEB1-expressing tumor stroma compared to tumor compartments.
• HDAC and DNA methylation inhibitors increased ZEB1 target gene expression.

Conclusions:

• ZEB1-mediated suppression of epithelial genes involves epigenetic modifications, specifically reduced histone acetylation.
• Targeting epigenetic modifications like histone acetylation and DNA methylation may offer therapeutic strategies to inhibit lung cancer metastasis.