YY1 negatively regulates the XAF1 gene expression in prostate cancer

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• XAF1 functions as a tumor suppressor gene, exhibiting reduced expression in various cancers.
• Reactivating XAF1 expression can inhibit tumor progression, highlighting the importance of understanding its silencing mechanisms.
• YY1 is a pleiotropic transcription factor implicated in cancer progression, and both YY1 and XAF1 are linked to adverse outcomes in prostate cancer (PCa).

Purpose of the Study:

• To investigate whether the transcription factor YY1 regulates the transcriptional activation of the XAF1 gene.
• To elucidate the molecular mechanisms underlying XAF1 silencing in prostate cancer.

Main Methods:

• Gene-reporter assays with site-directed mutagenesis to assess YY1's effect on XAF1.
• Chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) to detect YY1 binding to the XAF1 promoter.
• Analysis of gene expression data from The Cancer Genome Atlas (TCGA) consortium.

Main Results:

• YY1 was demonstrated to mediate XAF1 silencing through direct interaction with the XAF1 promoter in PCa cells.
• XAF1 expression was restored upon YY1 downregulation or inhibition of HDAC1, an enzyme crucial for YY1-mediated repression.
• Prostate cancer tissues exhibited lower XAF1 and higher HDAC1 expression compared to normal tissues.

Conclusions:

• YY1 acts as a transcriptional repressor of the tumor suppressor XAF1 in prostate cancer.
• The YY1-HDAC1 complex silences XAF1, contributing to prostate cancer progression.
• Targeting the YY1-HDAC1 pathway may represent a therapeutic strategy for prostate cancer.