Abstract 152: The long non-coding RNA HOTAIR affects exosome-mediated bladder cancer progression

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Exosomes are 30-100nM membrane-bound vesicles that participate in intercellular communication and facilitate tumor microenvironments. The mechanisms by which exosomes modify tumor niches are not fully understood. One possibility is that exosomes deliver biologically active molecules like mRNA, protein, miRNA and long non coding RNA (lncRNA) that alter the metabolism of recipient cells to produce pathological phenotypes. Exosomes may also activate the expression of genes involved in tumor progression in recipient cells. Overexpression of the lncRNA HOTAIR is associated with poor prognosis and affects tumor progression, in part, by recruiting PRC2 and LSD1 chromatin modifying complexes to thousands of target genes involved in tumor progression processes such as epithelial-to-mesenchyme transition (EMT). We show that HOTAIR is enriched in bladder cancer (BC) patient tumors and urinary exosomes. BC cell lines also express elevated levels of HOTAIR. Knockdown of HOTAIR in BC cell lines significantly reduces migration and invasion in trans-well and 3D culture, which correlates with EMT gene expression changes in these cells. Exosomes isolated from shHOTAIR vs shScramble cells fail to facilitate migration and invasion in 3D culture of a recipient BC cell line. Selected bands were isolated from a coomassie gel of shHOTAIR and shScramble exosomes and sent for mass spectrometry. Hundreds of putative proteins were identified including proteins involved in RNA binding, apoptosis, vesicle trafficking and integrins. These data support HOTAIR as an important player in exosome-mediated BC tumor progression possibly through affects on gene expression in exosome producer cells. For example, in shHOTAIR cells the loss of PRC2 and/or LSD1 complexes from key genes may ultimately affect the proteins available for packaging into exosomes. Exosomes have important roles in the tumor microenvironment and these data support a role for HOTAIR in the modulation of exosome-mediated tumor progression. Citation Format: Claudia Berrondo, Jonathan Flax, Edward M. Messing, Carla Beckham. The long non-coding RNA HOTAIR affects exosome-mediated bladder cancer progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 152. doi:10.1158/1538-7445.AM2015-152