A designed cell-permeable aptamer-based corepressor peptide is highly specific for the androgen receptor and inhibits...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Androgen receptor (AR) activity is crucial for prostate cancer progression.
• Current hormone therapies targeting AR can be limited by corepressor malfunction in castration-resistant prostate cancer.
• Overexpressing general corepressors can affect multiple transcription factors, necessitating AR-specific solutions.

Purpose of the Study:

• To identify and develop a novel AR-specific corepressor for inhibiting prostate cancer growth.
• To create a tool that specifically targets AR without affecting other nuclear receptors.
• To establish a potential vector-free therapeutic approach for prostate cancer.

Main Methods:

• Yeast peptide aptamer two-hybrid screen using full-length human AR.
• Identification of an AR-binding amino acid-stretch.
• Fusion of the aptamer to a silencing domain to create an aptamer-based corepressor (AB-CoR).
• Generation of a cell-permeable AB-CoR using a protein transduction domain.
• Testing AB-CoR activity in yeast, mammalian cells, and LNCaP prostate cancer cells.

Main Results:

• A novel amino acid-stretch specifically binds to the human AR, not progesterone or glucocorticoid receptors.
• The aptamer-based corepressor (AB-CoR) inhibits AR-mediated transactivation and PSA gene expression.
• Stable expression of AB-CoR suppresses LNCaP prostate cancer cell growth.
• Cell-permeable AB-CoR effectively inhibits AR activity and prostate cancer cell proliferation in a vector-free manner.

Conclusions:

• A novel AR-specific aptamer-based corepressor (AB-CoR) has been successfully developed.
• AB-CoR demonstrates efficacy in inhibiting AR signaling and prostate cancer cell growth.
• This aptamer-based approach offers a promising vector-free strategy for treating AR-dependent prostate cancer.