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Updated: Aug 18, 2026
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Small-interfering RNA-induced androgen receptor silencing leads to apoptotic cell death in prostate cancer
Xinbo Liao1, Siqing Tang, J Brantley Thrasher
1Department of Urology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA.
Abstract:
Prostate cancer is the second leading cause of cancer death in the United States and, thus far, there has been no effective therapy for the treatment of hormone-refractory disease. Recently, the androgen receptor (AR) has been shown to play a critical role in the development and progression of the disease. In this report, we showed that knocking down the AR protein level by a small interfering RNA (siRNA) approach resulted in a significant apoptotic cell death as evidenced by an increased annexin V binding, reduced mitochondrial potential, caspase-3/6 activation, and DFF45 and poly(ADP-ribose) polymerase cleavage. The apoptotic response was specifically observed in those siRNA-transfected cells that harbor a native AR gene. No cell death was found in the AR-null prostate cancer cell PC-3 or its subline that has been reconstituted with an exogenous AR gene, as well as two breast cancer cell lines that are AR positive. Moreover, in parallel with the siRNA-induced AR silencing, the antiapoptotic protein Bcl-xL was significantly reduced, which might account for the apoptotic cell death because ectopic enforced expression of Bcl-xL protein partially inhibited apoptosis after AR silencing. Taken together, our data showed that knocking down the AR protein level in prostate cancer cells leads to apoptosis by disrupting the Bcl-xL-mediated survival signal downstream of AR-dependent survival pathway.
Insights
Targeting the androgen receptor (AR) with small interfering RNA (siRNA) induces apoptosis in prostate cancer cells. This approach disrupts AR-dependent survival signals, offering a potential therapeutic strategy for hormone-refractory disease.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Prostate cancer is a leading cause of cancer death in the US.
- Effective therapies for hormone-refractory prostate cancer are lacking.
- The androgen receptor (AR) is critical in prostate cancer development and progression.
Purpose of the Study:
- To investigate the role of androgen receptor (AR) in prostate cancer cell survival.
- To determine if reducing AR protein levels can induce cancer cell death.
- To elucidate the molecular mechanisms underlying AR-mediated cell survival.
Main Methods:
- Utilized small interfering RNA (siRNA) to knockdown androgen receptor (AR) protein levels in prostate cancer cells.
- Assessed apoptosis through annexin V binding, mitochondrial potential, and caspase activation.
- Investigated the role of Bcl-xL in AR-dependent cell survival.
Main Results:
- siRNA-mediated AR knockdown significantly induced apoptotic cell death in AR-positive prostate cancer cells.
- Apoptosis was specific to cells with native AR expression; AR-null cells or those with exogenous AR did not undergo cell death.
- AR silencing led to reduced Bcl-xL expression, a key antiapoptotic protein, partially reversing apoptosis when Bcl-xL was overexpressed.
Conclusions:
- Reducing androgen receptor (AR) protein levels triggers apoptosis in prostate cancer cells.
- The apoptotic response is dependent on the presence of the AR gene.
- Disruption of the Bcl-xL-mediated survival pathway downstream of AR is a key mechanism for AR knockdown-induced apoptosis.
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