TY - JOUR
T1 - Subcellular localization of UC.8+ as a prognostic biomarker in bladder cancer tissue
AU - Terreri, Sara
AU - Mancinelli, Sara
AU - Ferro, Matteo
AU - Vitale, Maria Concetta
AU - Perdonà, Sisto
AU - Castaldo, Luigi
AU - Gigantino, Vincenzo
AU - Mercadante, Vincenzo
AU - De Cecio, Rossella
AU - Aquino, Gabriella
AU - Montella, Marco
AU - Angelini, Claudia
AU - Del Prete, Eugenio
AU - Aprile, Marianna
AU - Ciaramella, Angelo
AU - Liguori, Giovanna L.
AU - Costa, Valerio
AU - Calin, George A.
AU - Civita, Evelina La
AU - Terracciano, Daniela
AU - Febbraio, Ferdinando
AU - Cimmino, Amelia
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/2/2
Y1 - 2021/2/2
N2 - 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-tocytoplasmic 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.
AB - 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-tocytoplasmic 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.
KW - Bladder cancer
KW - Long noncoding RNA
KW - Prognostic biomarker
KW - Transcribed-ultraconserved region
KW - Ultraconserved region
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U2 - 10.3390/cancers13040681
DO - 10.3390/cancers13040681
M3 - Article
C2 - 33567603
AN - SCOPUS:85100532319
SN - 2072-6694
VL - 13
SP - 1
EP - 19
JO - Cancers
JF - Cancers
IS - 4
M1 - 681
ER -