title: Epigenetic changes and functional study of HOXA11 in human gastric cancer.
abstract: OBJECTIVE
  To examine epigenetic changes and the function of HOXA11 in human gastric cancer (GC).
  
  
  METHODS
  Seven GC cell lines, five cases of normal gastric mucosa and 112 cases primary GC samples were used in this study.
  
  
  RESULTS
  Expression of HOXA11 and lack of promoter region methylation were found in NCI-N87, MKN45, BGC823 and HGC27 cells. Loss of expression and complete methylation were found in AGS gastric cancer cells. Reduced expression and partial methylation were found in MGC803 and SGC7901 cells. Restoration of HOXA11 expression was induced by 5-aza-2'-deoxycytidine. HOXA11 was methylated in 81.25% (91/112) of primary GCs. The presence of methylation was associated with male gender, tumor size, tumor differentiation and lymph node metastasis (all p < 0.05). Restoration of HOXA11 expression reduced cell proliferation, invasion, migration and induced apoptosis and G2/M phase arrest. HOXA11 was found to inhibit Wnt signaling by upregulating NKD1 expression.
  
  
  CONCLUSIONS
  Epigenetic silencing of HOXA11 promotes GC proliferation, migration and invasion through activation of Wnt signaling.
authors.affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Cui
authors.forename: Dan
authors.initials: D
authors.lastname: Gao
authors.forename: Enqiang
authors.initials: E
authors.lastname: Linghu
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.forename: Runsheng
authors.initials: R
authors.lastname: Chen
authors.forename: Malcolm V
authors.initials: MV
authors.lastname: Brock
authors.forename: James G
authors.initials: JG
authors.lastname: Herman
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D060449:Wnt Signaling Pathway; D055815:Young Adult
chemical_list: C484298:HOXA11 protein, human; D018398:Homeodomain Proteins
keywords: 5-aza-2′-deoxycytidine; DNA methylation; HOXA11; NKD1; Wnt signaling pathway; epigenetics; gastric carcinoma; invasion; migration; tumor suppressor