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
U2 - 10.18632/oncotarget.2249
DO - 10.18632/oncotarget.2249
M3 - Article
C2 - 25216530
AN - SCOPUS:84907087674
SN - 1949-2553
VL - 5
SP - 7162
EP - 7171
JO - Oncotarget
JF - Oncotarget
IS - 16
ER -