Non-coding RNA transcripts originating from Ultraconserved Regions (UCRs) have tissue-specific expression and play relevant roles in the pathophysiology of multiple cancer types. Among them, we recently identified and characterized the ultra-conserved-transcript-8+ (uc.8+), whose levels correlate with grading and staging of bladder cancer. Here, to validate uc.8+ as a potential biomarker in bladder cancer, we assessed its expression and subcellular localization by using tissue microarray on 73 human bladder cancer specimens. We quantified uc.8+ by in-situ hybridization and correlated its expression levels with clinical characteristics and patient survival. The analysis of subcellular localization indicated the simultaneous presence of uc.8+ in the cytoplasm and nucleus of cells from the Low-Grade group, whereas a prevalent cytoplasmic localization was observed in samples from the High-Grade group, supporting the hypothesis of uc.8+ nuclear-to-cytoplasmic translocation in most malignant tumor forms. Moreover, analysis of uc.8+ expression and subcellular localization in tumor-surrounding stroma revealed a marked down-regulation of uc.8+ levels compared to the paired (adjacent) tumor region. Finally, deep machine-learning approaches identified nucleotide sequences associated with uc.8+ localization in nucleus and/or cytoplasm, allowing to predict possible RNA binding proteins associated with uc.8+, recognizing also sequences involved in mRNA cytoplasm-translocation. Our model suggests uc.8+ subcellular localization as a potential prognostic biomarker for bladder cancer.
Terreri Sara, Mancinelli Sara, Ferro Matteo, Vitale Maria Concetta, Perdonà Sisto, Castaldo Luigi, Gigantino Vincenzo, Mercadante Vincenzo, De Cecio Rossella, Aquino Gabriella, Montella Marco, Angelini Claudia, Del Prete Eugenio, Aprile Marianna, Ciaramella Angelo, Liguori Giovanna L, Costa Valerio, Calin George A, La Civita Evelina, Terracciano Daniela, Febbraio Ferdinando, Cimmino Amelia
bladder cancer, long noncoding RNA, prognostic biomarker, transcribed-ultraconserved region, ultraconserved region