Sox7 negatively regulates prostate-specific membrane antigen (PSMA) expression through PSMA-enhancer.

Area of Science:

• Molecular Biology
• Cancer Research
• Genetics

Background:

• Prostate-Specific Membrane Antigen (PSMA) expression in prostate epithelium is regulated by a cis-element known as the PSMA enhancer (PSME).
• PSME contains binding sites for Sox proteins, suggesting a role for these transcription factors in PSMA regulation.

Purpose of the Study:

• To identify Sox proteins that regulate PSMA expression.
• To elucidate the mechanism by which Sox7 interacts with PSME to control PSMA levels.

Main Methods:

• Statistical analysis of Sox7 and PSMA mRNA expression in prostate cancer datasets.
• In vitro and in vivo assays including chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), and luciferase reporter assays.
• Site-directed mutagenesis and expression studies in prostate cancer cell lines.

Main Results:

• Sox7 mRNA expression negatively correlated with PSMA mRNA in several prostate cancer studies.
• Canonical Sox7 protein directly binds to PSME at SOX box sites #2 and #4, suppressing PSMA transcription.
• The nuclear localization signal (NLS) regions of Sox7 are essential for its PSMA-suppressing activity.

Conclusions:

• Canonical Sox7 functions as a negative regulator of PSMA expression in prostate cancer.
• Inactivation of canonical Sox7 is linked to the upregulation of PSMA in non-metastatic prostate cancer.