Identification of Large Noncoding RNAs that Contribute to Prostate Cancer Progression

Abstract

Abstract : Large noncoding RNAs (lncRNAs) are pervasively transcribed in the genome, however their potential role in human diseases is poorly understood. In this study, we use RIP approach combined with RNAseq to capture lncRNAs from the genome-wide pool bound to androgen receptor in prostate cancer cells. We identify and confirm that PCGEM1 is an AR-binding partner. Next, to better evaluate the clinical relevance of PCGEM1, we examine its expression levels in a series of prostate tumor samples with different stage by quantitative RT-PCR. We found over all PCGEM1 is highly expressed in tumor samples with even higher expression in more aggressive tumor samples. We also explore the potential of PCGEM1 as aggressive prostate cancer biomarkers by detecting and quantify levels of PCGEM1 in situ on clinical specimen together with AR. We found colocalization signal of PCGEM1 and AR is correlated with tumor aggressiveness. Finally, overexpression and knockdown studies reveal that PCGEM1 plays a role in prostate cancer cells growth and drug resistance. More importantly, PCGEM1 is able to activate AR-mediated transcription. Taken together, the remarkable interaction of PCGEM1 with AR and its elevated expression in a significant percentage of tumor tissues suggest specific functions and clinical significance of PCGEM1 in prostate cancer progression.