Subcellular Localization of Uc.8+ As a Prognostic Biomarker in Bladder Cancer Tissue

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Feb 11

PMID 33567603

Citations 7

Authors

Sara Terreri

Sara Mancinelli

Matteo Ferro

Maria Concetta Vitale

Sisto Perdona

Luigi Castaldo

Vincenzo Gigantino

Vincenzo Mercadante

Rossella De Cecio

Gabriella Aquino

Marco Montella

Claudia Angelini

Eugenio Del Prete

Marianna Aprile

Angelo Ciaramella

Giovanna L Liguori

Valerio Costa

George A Calin

Evelina La Civita

Daniela Terracciano

Ferdinando Febbraio

Amelia Cimmino

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

New Challenges in Bladder Cancer Diagnosis: How Biosensing Tools Can Lead to Population Screening Opportunities.

Tortora F, Guastaferro A, Barbato S, Febbraio F, Cimmino A Sensors (Basel). 2025; 24(24.

PMID: 39771612 PMC: 11679013. DOI: 10.3390/s24247873.

Ultra-conserved RNA: a novel biological tool with diagnostic and therapeutic potential.

Wang T, Li F, Lu Z Discov Oncol. 2023; 14(1):41.

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Emerging RNA-Based Therapeutic and Diagnostic Options: Recent Advances and Future Challenges in Genitourinary Cancers.

Tortora F, La Civita E, Trivedi P, Febbraio F, Terracciano D, Cimmino A Int J Mol Sci. 2023; 24(5).

PMID: 36902032 PMC: 10003365. DOI: 10.3390/ijms24054601.

A new biomarker panel of ultraconserved long non-coding RNAs for bladder cancer prognosis by a machine learning based methodology.

Ciaramella A, Di Nardo E, Terracciano D, Conte L, Febbraio F, Cimmino A BMC Bioinformatics. 2023; 23(Suppl 6):569.

PMID: 36879192 PMC: 9987036. DOI: 10.1186/s12859-023-05167-6.

Transcribed Ultraconserved Regions: New regulators in cancer signaling and potential biomarkers.

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