Ogy. Author manuscript; offered in PMC 2014 May perhaps 01.Published in final edited
Ogy. Author manuscript; accessible in PMC 2014 May possibly 01.Published in final edited type as: Gastroenterology. 2013 May possibly ; 144(five): 95666.e4. doi:ten.1053j.gastro.2013.01.019.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptHypomethylation of Noncoding DNA Regions and OvereNOS Storage & Stability expression in the Lengthy Noncoding RNA, AFAP1-AS1, in Barrett’s Esophagus and Esophageal AdenocarcinomaWenjing Wu1,2,, 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 associated with Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). Dys-regulation of noncoding RNAs occurs throughout carcinogen-esis but has by no means been studied in BE or EAC. We applied high-resolution methylome analysis to recognize alterations at genomic regions that encode noncoding RNAs in BE and EAC. METHODS–We analyzed methylation of 1.8 million CpG web-sites applying massively parallel sequencing-based Assistance tagging in matched EAC, BE, and regular esophageal tissues. We also analyzed human EAC (OE33, SKGT4, and FLO-1) and regular (HEEpic) esophageal cells. RESULTS–BE and EAC exhibited genome-wide hypomethylation, considerably affecting intragenic and repetitive genomic elements too as noncoding regions. These methylation changes targeted compact and lengthy noncoding regions, discriminating normal from matched BE or EAC tissues. One lengthy noncoding RNA, AFAP1-AS1, was very hypomethylated and overexpressed in BE and EAC tissues and EAC cells. Its silencing by little interfering RNA inhibited proliferation and colony-forming capacity, induced apoptosis, and decreased EAC cell migration and invasion without altering the expression of its protein-coding counterpart, AFAP1.2013 by the AGA ERK5 manufacturer InstituteReprint requests, Address requests for reprints to: Stephen J. Meltzer, MD, The Johns Hopkins University School of Medicine, 1503 East Jefferson Street, Area 112, Baltimore, Maryland 21287; smeltzerjhmi.edu. (410) 502-1329; or Amit Verma, MB, BS, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Chanin Constructing, Space 302B, Bronx, New York 10461. amit.vermaeinstein.yu.edu. Authors share co-first authorship. Conflicts of interest The authors disclose no conflicts.Supplementary Material Note: To access the supplementary material accompanying this short article, take a look at the on the internet version of Gastroenterology at gastrojournal.org, and at http:dx.doi.org10.1053j.gastro.2013.01.019.Wu et al.PageCONCLUSIONS–BE and EAC exhibit lowered methylation that consists of noncoding regions. Methylation with the long noncoding RNA AFAP1-AS1 is decreased in BE and EAC, and its expression inhibits cancer-related biologic functions of EAC cells. Keywords Esophageal Cancer Progression; Tumor Development; Gene Regulation; Noncoding RNA Esophageal adenocarcinoma (EAC) is one of the fastest-growing cancers within the Western world. Ninety-five % of EA.
