Integrative Analysis Of Functional Long Noncoding Rnas During Prostate Cancer Progression

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Prostate cancer progression from an androgen-dependent state to an androgen-independent phase, which is also referred to castration-resistant prostate cancer (CRPC), not only results in cancer refractory to androgen deprivation therapy but also marks its lethal prognosis. However, it remains largely unknown that how CRPC develops. As a result, ideal diagnosis and therapeutic tools are still highly in demand and under investigation. Recently, many studies indicate that long non-coding RNA (lncRNA) can be extensively functional rather than just transcriptional noise and lncRNAs are also widely involved in the pathogenesis of different types of cancers. To identify and characterize functional lncRNAs during prostate cancer progression, we firstly developed an integrative computational strategy for predicting lncRNAs that may be functionally important for tumorigenesis or tumor suppression via analysis of lncRNA expression profiles, clinical information and somatic genomic alteration profiles of tumor samples. By applying this approach, we predicted a cohort of lncRNAs that may be clinically important for prostate tumorigenesis and experimentally confirmed two functional lncRNAs - PCAT6 and PCAT7 in prostate cancer cell line model. Work from others and our lab have also shown that both androgen receptor (AR) and polycomb group protein enhancer of zest 2 (EZH2) play pivotal roles during prostate cancer progression to CRPC. In contrast to protein coding genes, little is known about AR or EZH2 regulated lncRNAs during this process. To this purpose, we also performed RNAseq in prostate cancer cell lines and combined ChIPseq data to identify androgen-regulated and AR/EZH2-regulated lncRNAs. These regulated lncRNAs are also intersected with above clinically significant lncRNA list to narrow down interesting hits for follow-up mechanistic studies. Our integrative approach has successfully identified a cohort of potentially functional lncRNAs which hold great potentials to be novel prognostic biomarkers and/or therapeutic targets for treatment of advanced prostate cancer. Citation Format: Teng Fei, Yiwen Chen, Zhou Du, Xiaole Shirley Liu, Myles Brown. Integrative analysis of functional long noncoding RNAs during prostate cancer progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5238. doi:10.1158/1538-7445.AM2014-5238