title: Hypomethylation of noncoding DNA regions and overexpression of the long noncoding RNA, AFAP1-AS1, in Barrett's esophagus and esophageal adenocarcinoma.
abstract: OBJECTIVE
  Alterations in methylation of protein-coding genes are associated with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Dysregulation of noncoding RNAs occurs during carcinogenesis but has never been studied in BE or EAC. We applied high-resolution methylome analysis to identify changes at genomic regions that encode noncoding RNAs in BE and EAC.
  
  
  METHODS
  We analyzed methylation of 1.8 million CpG sites using massively parallel sequencing-based HELP tagging in matched EAC, BE, and normal esophageal tissues. We also analyzed human EAC (OE33, SKGT4, and FLO-1) and normal (HEEpic) esophageal cells.
  
  
  RESULTS
  BE and EAC exhibited genome-wide hypomethylation, significantly affecting intragenic and repetitive genomic elements as well as noncoding regions. These methylation changes targeted small and long noncoding regions, discriminating normal from matched BE or EAC tissues. One long noncoding RNA, AFAP1-AS1, was extremely hypomethylated and overexpressed in BE and EAC tissues and EAC cells. Its silencing by small interfering RNA inhibited proliferation and colony-forming ability, induced apoptosis, and reduced EAC cell migration and invasion without altering the expression of its protein-coding counterpart, AFAP1.
  
  
  CONCLUSIONS
  BE and EAC exhibit reduced methylation that includes noncoding regions. Methylation of the long noncoding RNA AFAP1-AS1 is reduced in BE and EAC, and its expression inhibits cancer-related biologic functions of EAC cells.
authors: Center for Laboratory Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors: Wenjing
authors: W
authors: Wu
authors: Tushar D
authors: TD
authors: Bhagat
authors: Xue
authors: X
authors: Yang
authors: Jee Hoon
authors: JH
authors: Song
authors: Yulan
authors: Y
authors: Cheng
authors: Rachana
authors: R
authors: Agarwal
authors: John M
authors: JM
authors: Abraham
authors: Sariat
authors: S
authors: Ibrahim
authors: Matthias
authors: M
authors: Bartenstein
authors: Zulfiqar
authors: Z
authors: Hussain
authors: Masako
authors: M
authors: Suzuki
authors: Yiting
authors: Y
authors: Yu
authors: Wei
authors: W
authors: Chen
authors: Charis
authors: C
authors: Eng
authors: John
authors: J
authors: Greally
authors: Amit
authors: A
authors: Verma
authors: Stephen J
authors: SJ
authors: Meltzer
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001471:Barrett Esophagus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C497360:AFAP1 protein, human; D004273:DNA, Neoplasm; D008840:Microfilament Proteins; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering