Abstract 1120: Identification and characterization of a novel androgen-regulated long non-coding RNA in prostate cancer.

Abstract

Abstract Long non-coding RNAs (lncRNAs) have recently been associated with the development and progression of a variety of cancers, including prostate cancer. However, to date very few prostate cancer lncRNAs have been characterized by functional studies as bona fide oncogenes and tumor suppressors. Previously, transcriptome sequencing (RNA-Seq) of prostate tumors and benign adjacency tissues revealed a set of putative lncRNAs termed Prostate Cancer Associated Transcripts (PCATs) with significantly altered expression levels in cancer. Intriguingly, a subset of these PCATs were strikingly upregulated in treatment-resistant metastatic prostate cancer samples, suggesting that they may play a role in the development of castrate resistant disease. To explore this possibility we stimulated prostate cancer cell lines with synthetic androgen and monitored the responsiveness of several PCATs. We found that PCAT29, a six-exon nuclear transcript located in a gene desert on chromosome 15, was suppressed by androgen in a time-dependent fashion. Furthermore, androgen receptor (AR) ChIP-Seq data revealed a strong binding site upstream of the PCAT29 promoter suggesting that PCAT29 may be a direct androgen receptor target. Supporting this notion, physical castration of a mouse Xenograft model led to profound upregulation of PCAT29 suggesting that AR signaling suppresses its transcription. Knockdown of PCAT29 using two independent shRNA leads to significant increase in the proliferation of LNCaP cells. Consistently, overexpression of PCAT29 in DU145 cells suppresses proliferation. Finally, we show that in prostate cancer patients, high PCAT29 expression correlates with better overall survival. Taken together our study suggests that PCAT29 may have a tumor suppressor like function in prostate cancer. Ongoing studies are focused on understanding the potential mechanism of PCAT29 function and its relationship with androgen signaling. Citation Format: Rohit Malik, Matthew K. Iyer, John R. Prensner, Lalit Patel, Sumin Han, Wei Chen, Felix Feng, Arul M. Chinnaiyan. Identification and characterization of a novel androgen-regulated long non-coding RNA in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1120. doi:10.1158/1538-7445.AM2013-1120