Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis

Fassan, M. et al. (2014) Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis. Oncotarget, 5(16), pp. 7162-7171. (doi: 10.18632/oncotarget.2249) (PMID:25216530) (PMCID:PMC4196192)

Abstract

Barrett’s esophagus (BE) involves a metaplastic replacement of native esophageal squamous epithelium (Sq) by columnar-intestinalized mucosa, and it is the main risk factor for Barrett-related adenocarcinoma (BAc). Ultra-conserved regions (UCRs) are a class non-coding sequences that are conserved in humans, mice and rats. More than 90% of UCRs are transcribed (T-UCRs) in normal tissues, and are altered at transcriptional level in tumorigenesis. To identify the T-UCR profiles that are dysregulated in Barrett’s mucosa transformation, microarray analysis was performed on a discovery set of 51 macro-dissected samples obtained from 14 long-segment BE patients. Results were validated in an independent series of esophageal biopsy/surgery specimens and in two murine models of Barrett’s esophagus (i.e. esophagogastric-duodenal anastomosis). Progression from normal to BE to adenocarcinoma was each associated with specific and mutually exclusive T-UCR signatures that included up-regulation of uc.58-, uc.202-, uc.207-, and uc.223- and down-regulation of uc.214+. A 9 T-UCR signature characterized BE versus Sq (with the down-regulation of uc.161-, uc.165-, and uc.327-, and the up-regulation of uc.153-, uc.158-, uc.206-, uc.274-, uc.472-, and uc.473-). Analogous BE-specific T-UCR profiles were shared by human and murine lesions. This study is the first demonstration of a role for T-UCRs in the transformation of Barrett’s mucosa.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Braconi, Professor Chiara and Valeri, Dr Nicola
• Authors: Fassan, M., Dall’Olmo, L., Galasso, M., Braconi, C., Pizzi, M., Realdon, S., Volinia, S., Valeri, N., Gasparini, P., Baffa, R., Souza, R. F., Vicentini, C., D'Angelo, E., Bornschein, J., Nuovo, G. J., Zaninotto, G., Croce, C. M., and Rugge, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Oncotarget
• Publisher: Impact Journals
• ISSN: 1949-2553
• ISSN (Online): 1949-2553
• Published Online: 23 July 2014
• Copyright Holders: Copyright © 2014 The Authors
• First Published: First published in Oncotarget 5(16): 7162-7171
• Publisher Policy: Reproduced under a Creative Commons License