Abstract B31: Bladder cancer patient urinary exosomes and tumors contain long noncoding RNA that may serve as therapeutic targets and biomarkers

Abstract

Abstract While long non-coding RNA (lncRNA) play important roles in tumor biology including bladder cancer (BC), no previous studies have shown that lncRNAs in BC patient urinary exosomes (UEs) can function as biomarkers of disease. Exosomes are 30-150nm secreted membrane-bound vesicles that contain active biomolecules like: messenger(m)RNA, micro(mi)RNA, lncRNA and proteins generated from their cells of origin. In this study, we identified a panel of lncRNAs and mRNAs enriched in the UEs and tumors of BC patients, including the well-characterized lncRNA, HOTAIR. In order to elucidate if HOTAIR has a functional role in BC, we knocked it down in BC cell lines. Loss of HOTAIR resulted in reduced expression of known HOTAIR epithelial-to-mesenchyme transition (EMT) target genes, as well as reduced migration, and invasion using trans-well and 3-D culture assays. These data suggest that HOTAIR may serve as both a biomarker in UEs and as a potential therapeutic target. Critically, we RNA-Sequenced primary tumors, distal normal tissue (DNT) and UEs of BC patients and UEs from healthy volunteers (HV) to identify two novel lncRNAs, LINC00477 and LINC00940 enriched in BC patients' UEs and tumors. These candidate lncRNAs were confirmed with quantitative real time (qRT-PCR). Taken together, UE lncRNA content reflect the lncRNA content of BC tumors and may serve as biomarkers of disease. Further investigation is needed to validate the use of the lncRNAs presented in this study as biomarkers and putative therapeutic targets in relevant patient populations. Citation Format: Claudia Berrondo, Jonathan Flax, Aisha Siebert, Victor Kucherov, Alex Rosenberg, Christopher Fucile, Carla Beckham. Bladder cancer patient urinary exosomes and tumors contain long noncoding RNA that may serve as therapeutic targets and biomarkers. [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 B31.