Abstract IA11: Dependency of prostate cancer on HNRNPL and its associated RNAs

Abstract

Abstract RNA binding proteins (RBPs) play critical roles in RNA metabolism and underlie multiple cellular functions. However, how RBPs act in cancer remains obscure. Using an RBP-focused RNAi screen and a genome-wide CRISPR/Cas9 knockout screen, we identified HNRNPL as an RBP required for prostate cancer growth. To understand the HNRNPL function mechanistically, we profiled the HNRNPL-bound RNA landscape by RIP-seq and linked these RBP-RNA interactions to multiple RNA regulatory processes. HNRNPL directly regulates the alternative splicing of a set of associated RNAs, including those encoding the androgen receptor (AR), the key lineage-specific prostate cancer oncogene. Interestingly, HNRNPL also regulates circular RNA formation. Moreover, we identified LARP, a novel HNRNPL-associated long noncoding RNA (lncRNA), as a cofactor of HNRNPL's gene regulatory function. Collectively, our data reveal HNRNPL and its RNA partners as novel players in prostate cancer growth, suggesting the potential to target RBPs or RBP-RNA interactions therapeutically. Citation Format: Teng Fei, Yiwen Chen, Myles Brown, X. Shirley Liu. Dependency of prostate cancer on HNRNPL and its associated RNAs. [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 IA11.