Login to Access Video or Poster Abstract: MP99-19
Sources of Funding: none

Introduction

The androgen receptor (AR) plays an important role in the progression of prostate cancer (PCa) before and after the castration-resistant stages. Androgen-deprivation therapy (ADT) has become a key treatment for advanced PCa. Although ADT initially achieves significant clinical response, PCa eventually relapses and progresses into castration-resistant prostate cancer (CRPC), a more aggressive form of PCa characterized by the resistance to ADT manipulation. Recent studies have demonstrated that remaining AR remains critical to the development of CRPC. Therefore, better dissecting the mechanism(s) underlying the targeting AR in CRPC would hold promise for overcoming the challenge of CRPC treatment.

Methods

LNCaP, DU145 and C4-2 were employed in this study. A series of cell and tumor, biochemical, molecular biologic assays such as UV Cross-Linking and Immunoprecipitation (CLIP) assay?RNA Immunoprecipitation, TUNEL assay?RNA-pull down assay, Proliferation assay, Luciferase assay were carried out.

Results

We found that GAS5, a long non-coding RNA (lncRNA), could interact and suppress AR transactivation in castration resistant PCa C4-2 cells. Targeting lncRNA-GAS5 by siRNA enhanced the expression of AR target gene PSA via alteration of AR recruitment to the PSA promoter. The consequences of suppression of AR transactivation led to suppress cell proliferation and enhance cell apoptosis in C4-2 cells in the castration resistant condition. In return, the suppressed AR could also modulate the lncRNA-GAS5 expression in a feedback regulation mechanism._x000D_ the figure shows GAS5 was downregulated in clinical CRPC specimen compared to primary PCa samples. A gene expression microarray dataset (GSE22606) deposited in public database was analyzed, where n denotes the mumble of total samples and p stands for the adjusted R statistical p value.

Conclusions

These results revealed that LncRNA-GAS5 might play important roles to target the remaining AR signals in PCa at the castration resistant stage and targeting LncRNA-GAS5 to alter these remaining AR signals in CRPC.

Funding

none