Abstract A027: Identification and characterization of PLUTO-201, a novel lncRNA associated with prostate cancer metastasis

Abstract Prostate cancer is the most common non-cutaneous malignancy in men, accounting for approximately 268,000 cases and 35,000 deaths in the United States each year. This disease is a heterogeneous entity with a wide spectrum of clinical behaviors and outcomes - while a majority of men will be cured of early-stage prostate cancer, approximately 20% will develop metastatic disease, which is incurable and ultimately fatal. Despite extensive investigation, the factors promoting aggressive prostate cancer are incompletely understood. Using recently reported microarray data representing a comprehensive analysis of lncRNA prevalence across thousands of patients with prostate cancer, we now report the identification of a novel lncRNA, Prostate Locus of Uncharacterized Transcript Outlier 201 (PLUTO-201), which is strongly associated with metastasis and poor overall survival in men with prostate cancer. We find that in vitro manipulation of PLUTO-201 expression levels in prostate cancer cell lines modulates proliferation rates and markers of aggressive phenotype. Further investigation shows that PLUTO-201 localizes to the nucleus and regulates transcription of multiple genes including those responsible for steroid biosynthesis and the MHC class 1 complex, driving increased growth in androgen-depleted conditions and decreased susceptibility to T cell-mediated cytotoxicity. Overall, our findings nominate PLUTO-201 as a driver of aggressive prostate cancer phenotypes and poor clinical outcomes and suggest possible mechanisms accounting for this activity. Citation Format: Haolong Li, Noah Younger, Hyun Jin Shin, Bhavna Malik, Shuang G. Zhao, Sethuramasundaram Pitchiaya, Marsha Calvert, Meng Zhang, Laura Chang, Lisa Chesner, Junjie Hua, Kathy Li, Vishal Kothari, Emily Egusa, Jonathan Chou, Rajdeep Das, Alma Burlingame, Arul M. Chinnaiyan, Hui Li, Felix Y. Feng. Identification and characterization of PLUTO-201, a novel lncRNA associated with prostate cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A027.