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 - Funding Information:
This research was funded by SATIN-POR CAMPANIA FESR 2014/2020 to A.C., V.C. and G.L.L. The V.C. Unit was funded by My First AIRC Grant (MFAG) Programme (grant n. 23453). G.L.L received financial support from the VES4US project funded by the European Union?s Horizon 2020 research and innovation programme under grant agreement No 801338.
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
AN - SCOPUS:85100532319
SN - 2072-6694
VL - 13
SP - 1
EP - 19
JO - Cancers
JF - Cancers
IS - 4
M1 - 681
ER -