Abstract A22: Functional long noncoding RNAs in castration-resistant prostate cancer

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 lethal prognosis. Androgen receptor (AR) plays central roles in both normal prostate development and prostate cancer progression. Aberrant androgen/AR signaling activity is often associated with the development of CRPC, such as increased synthesis of steroid hormone, increased expression of AR, emergence of specific AR variants etc. However, deeper understanding of detailed mechanism of CRPC development is still necessary in order to discover novel effective drug targets for the treatment of CRPC. Recent studies suggest 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 including prostate cancer. To further investigate the potential role of lncRNAs during prostate cancer progression, we profiled lncRNA transcriptome using RNA-seq in prostate cancer cells in the presence or absence of androgen treatment. In combination with AR cistrome data, we identified a set of lncRNAs that are directly regulated by androgen/AR signaling. A specific lncRNA was identified as androgen/AR repressed target gene in androgen-dependent cells while showing significant higher expression in androgen-independent cells that mimics CRPC state. Interestingly, knockdown of this lncRNA specifically attenuates the growth of androgen-independent cells while has little effect on androgen-dependent cells. To understand the detailed mechanism, we identified the downstream target genes using RNA-seq upon silencing this lncRNA in either androgen-dependent or -independent cells. Moreover, this lncRNA is located in a region that is frequently amplified in CRPC and highly expressed in a subset of CRPC patients. We suggest that this lncRNA, along with other androgen/AR targets, may play a role during the development of CRPC and could serve as a potential drug target for the treatment of CRPC. Note: This abstract was not presented at the conference. Citation Format: Teng Fei, Yiwen Chen, Xiaole Shirley Liu, Myles Brown. Functional long noncoding RNAs in castration-resistant prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A22.