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

Matteo Fassan, Luigi Dall'Olmo, Marco Galasso, Chiara Braconi, Marco Pizzi, Stefano Realdon, Stefano Volinia, Nicola Valeri, Pierluigi Gasparini, Raffaele Baffa, Rhonda F. Souza, Caterina Vicentini, Edoardo D'Angelo, Jan Bornschein, Gerard J. Nuovo, Giovanni Zaninotto, Carlo M. Croce, Massimo Rugge

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7162-7171
Number of pages10
JournalOncotarget
Volume5
Issue number16
StatePublished - 2014

Fingerprint

Untranslated RNA
Barrett Esophagus
Carcinogenesis
Mucous Membrane
Adenocarcinoma
Up-Regulation
Down-Regulation
Conserved Sequence
Microarray Analysis
Epithelium
Biopsy

Keywords

  • Barrett's carcinogenesis
  • Barrett's esophagus
  • Expression signature
  • T-UCRs

ASJC Scopus subject areas

  • Oncology

Cite this

Fassan, M., Dall'Olmo, L., Galasso, M., Braconi, C., Pizzi, M., Realdon, S., ... Rugge, M. (2014). Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis. Oncotarget, 5(16), 7162-7171.

Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis. / Fassan, Matteo; Dall'Olmo, Luigi; Galasso, Marco; Braconi, Chiara; Pizzi, Marco; Realdon, Stefano; Volinia, Stefano; Valeri, Nicola; Gasparini, Pierluigi; Baffa, Raffaele; Souza, Rhonda F.; Vicentini, Caterina; D'Angelo, Edoardo; Bornschein, Jan; Nuovo, Gerard J.; Zaninotto, Giovanni; Croce, Carlo M.; Rugge, Massimo.

In: Oncotarget, Vol. 5, No. 16, 2014, p. 7162-7171.

Research output: Contribution to journalArticle

Fassan, M, Dall'Olmo, L, Galasso, M, Braconi, C, Pizzi, M, Realdon, S, Volinia, S, Valeri, N, Gasparini, P, Baffa, R, Souza, RF, Vicentini, C, D'Angelo, E, Bornschein, J, Nuovo, GJ, Zaninotto, G, Croce, CM & Rugge, M 2014, 'Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis', Oncotarget, vol. 5, no. 16, pp. 7162-7171.
Fassan M, Dall'Olmo L, Galasso M, Braconi C, Pizzi M, Realdon S et al. Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis. Oncotarget. 2014;5(16):7162-7171.
Fassan, Matteo ; Dall'Olmo, Luigi ; Galasso, Marco ; Braconi, Chiara ; Pizzi, Marco ; Realdon, Stefano ; Volinia, Stefano ; Valeri, Nicola ; Gasparini, Pierluigi ; Baffa, Raffaele ; Souza, Rhonda F. ; Vicentini, Caterina ; D'Angelo, Edoardo ; Bornschein, Jan ; Nuovo, Gerard J. ; Zaninotto, Giovanni ; Croce, Carlo M. ; Rugge, Massimo. / Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis. In: Oncotarget. 2014 ; Vol. 5, No. 16. pp. 7162-7171.
@article{5cc435d2acb44aaeba49d532101b1017,
title = "Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis",
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.",
keywords = "Barrett's carcinogenesis, Barrett's esophagus, Expression signature, T-UCRs",
author = "Matteo Fassan and Luigi Dall'Olmo and Marco Galasso and Chiara Braconi and Marco Pizzi and Stefano Realdon and Stefano Volinia and Nicola Valeri and Pierluigi Gasparini and Raffaele Baffa and Souza, {Rhonda F.} and Caterina Vicentini and Edoardo D'Angelo and Jan Bornschein and Nuovo, {Gerard J.} and Giovanni Zaninotto and Croce, {Carlo M.} and Massimo Rugge",
year = "2014",
language = "English (US)",
volume = "5",
pages = "7162--7171",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "16",

}

TY - JOUR

T1 - Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis

AU - Fassan, Matteo

AU - Dall'Olmo, Luigi

AU - Galasso, Marco

AU - Braconi, Chiara

AU - Pizzi, Marco

AU - Realdon, Stefano

AU - Volinia, Stefano

AU - Valeri, Nicola

AU - Gasparini, Pierluigi

AU - Baffa, Raffaele

AU - Souza, Rhonda F.

AU - Vicentini, Caterina

AU - D'Angelo, Edoardo

AU - Bornschein, Jan

AU - Nuovo, Gerard J.

AU - Zaninotto, Giovanni

AU - Croce, Carlo M.

AU - Rugge, Massimo

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Barrett's carcinogenesis

KW - Barrett's esophagus

KW - Expression signature

KW - T-UCRs

UR - http://www.scopus.com/inward/record.url?scp=84907087674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907087674&partnerID=8YFLogxK

M3 - Article

C2 - 25216530

AN - SCOPUS:84907087674

VL - 5

SP - 7162

EP - 7171

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 16

ER -