Group, South San Francisco, CA, USA. The authors would also prefer to acknowledge the contribution of Dana Aeschliman in conducting the analyses. Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche Ltd. Conflict of interest AG, JV and BL are Genentech workers and own Roche stock. JL was formerly employed by Genentech, is at present employed by MedImmune and owns Roche stock. MB is actually a Roche employee and owns Roche stock. EC is really a Roche employee and owns AstraZeneca stock. AK is actually a Roche employee. TJC has received consultancy fees from Pharsight. JFM has received consultancy costs and charges for evaluation activities from Pharsight. JC is a consultant for Roche, Celgene, and Novartis and has received speaker honoraria from Roche, Novartis, Celgene, and Eisai. All authors had complete handle of all key information, which are accessible for assessment upon request. Open Access This short article is distributed below the terms of your Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, supplied the original author(s) and also the supply are credited.
NIH Public AccessAuthor ManuscriptGastroenterology. Author manuscript; out there in PMC 2014 May 01.Published in final edited form as: Gastroenterology. 2013 Might ; 144(5): 956?66.e4. doi:10.1053/j.gastro.2013.01.019.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptHypomethylation of Noncoding DNA Regions and Overexpression with the Long Noncoding RNA, AFAP1-AS1, in Barrett’s Esophagus and Esophageal AdenocarcinomaWenjing Wu1,two,*, Tushar D. Bhagat3,*, Xue Yang2, Jee Hoon Song2, Yulan Cheng2, Rachana Agarwal2, John M. Abraham2, Sariat Ibrahim2, Matthias Bartenstein3, Zulfiqar Hussain3, Masako Suzuki3, Yiting Yu3, Wei Chen1, Charis Eng4, John Greally3, Amit Verma3, and Stephen J. Meltzer2 for Laboratory Medicine, The very first Affiliated Hospital, College of Medicine, Xi’an Jiaotong University, Xi’an, China 2Division of Gastroenterology, Departments of Medicine and Oncology and Sidney Kimmel Extensive Cancer Center, The Johns Hopkins University College of Medicine, Baltimore, Maryland 3Albert Einstein College of Medicine, Bronx, New York 4Cleveland Clinic, Cleveland, Ohio1CenterAbstractBACKGROUND AIMS–Alterations in methylation of protein-coding genes are related with Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC).84793-07-7 web Dys-regulation of noncoding RNAs happens during carcinogen-esis but has by no means been studied in BE or EAC. We applied high-resolution methylome evaluation to determine alterations at genomic regions that encode noncoding RNAs in BE and EAC.1053656-76-0 Formula METHODS–We analyzed methylation of 1.PMID:24455443 eight million CpG internet sites applying massively parallel sequencing-based Support tagging in matched EAC, BE, and typical esophageal tissues. We also analyzed human EAC (OE33, SKGT4, and FLO-1) and standard (HEEpic) esophageal cells. RESULTS–BE and EAC exhibited genome-wide hypomethylation, significantly affecting intragenic and repetitive genomic elements also as noncoding regions. These methylation alterations targeted compact and lengthy noncoding regions, discriminating standard from matched BE or EAC tissues. One lengthy noncoding RNA, AFAP1-AS1, was really hypomethylated and overexpressed in BE and EAC tissues and EAC cells. Its silencing by compact interfering RNA inhibited proliferation and colony-forming capacity, induced apoptosis, and reduced EAC cell migration and invasion devoid of altering the expression of its protein-coding counter.
