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Updated: Feb 1, 2026
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
YY1 negatively regulates the XAF1 gene expression in prostate cancer
B Camacho-Moctezuma1, M Quevedo-Castillo1, J Melendez-Zajgla2
1Laboratorio de Investigacion en Patologia Experimental, Hospital Infantil de Mexico Federico Gomez, 06720, Mexico City, Mexico; Division de Investigacion, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, 04510, Mexico City, Mexico.
Abstract:
XAF1 is a tumor suppressor gene with low or absent expression in cancer. Since transcriptional reactivation or ectopic-mediated expression of XAF1 inhibits tumor growth, it is of great interest to elucidate the molecular mechanisms leading to XAF1 silencing. YY1 is a transcription factor that acts as a repressor or an activator to modulate several cancer-associated cellular processes. Both YY1 and XAF1 have key roles in prostate cancer (PCa) progression and are associated with worse clinical outcomes. To assess whether YY1 regulates the transcriptional activation of the XAF1 gene, we performed gene-reporter assays coupled with site-directed mutagenesis, which showed that YY1 is able to mediate XAF1 silencing. Concordantly, ChIP-qPCR assays showed that YY1 interacts with the XAF1 promoter in PC3 cells that lacks XAF1 expression. This association was lost after exposure to epigenetic modulators that induce XAF1 expression. Further supporting the YY1's repressive role, we found transcriptional reactivation of the XAF1 gene by YY1 downregulation. As expected by previous reports showing that HDAC1 is needed for YY1-mediated repressive actions, we observed XAF1 re-expression after either inhibition or downregulation of the HDAC1 gene. Finally, expression data retrieved from the TCGA consortium showed that PCa samples presented lower XAF1 and higher HDAC expression levels than normal tissues. Thus, our results support a model in which YY1 is able to silence tumor suppressor genes such as XAF1 through HDAC1 in PCa.
Insights
The transcription factor YY1 silences the tumor suppressor XAF1 in prostate cancer by interacting with its promoter, a process involving HDAC1. Reactivating XAF1 expression is crucial for inhibiting tumor growth.
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.
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