title: HOXA11 gene is hypermethylation and aberrant expression in gastric cancer.
abstract: BACKGROUND
  Aberrant DNA methylation is an acquired epigenetic alteration that serves as an alternative to genetic defects in the inactivation of tumor suppressor genes and other genes in diverse human cancers. Gastric carcinoma is one of the tumors with a high frequency of aberrant methylation in promoter region. Hence we investigated the promoter methylation status and expression level of HOXA11 gene which may involve in GC development.
  
  
  METHODS
  Thirty-two surgical excised gastric cancer specimens, twelve paired adjacent non-cancerous specimens and seven normal gastric mucosas were examined. The methylation status and expression level of HOXA11 gene were determined by bisulfite sequencing polymerase chain reaction (BSP), real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) respectively. HOXA11 expression was knocked-down with siRNA to mimic HOXA11 gene hypermethylation and ability of cell proliferation and migration was determinate. In addition, we analyzed and correlated the findings with clinicopathological features.
  
  
  RESULTS
  The methylation level of HOXA11 gene in gastric cancer tissues and adjacent non-cancerous tissues were higher than those in normal gastric mucosa (P < 0.05). The methylation level was higher in TNM III and IV patients of GC than those in TNM I and II patients (P < 0.05). The expression of HOXA11 mRNA and protein decreased in normal gastric mucosa, peri-cancer tissue and GC (P < 0.05). HOXA11 expression was inversely correlated with DNA methylation (P < 0.05). Knocked-down of HOXA11 expression with siRNA in BGC-823 cells enhanced cell proliferation compared with control, but no significant different was observed in migration ability.
  
  
  CONCLUSIONS
  Hypermethylation and decreased expression of HOXA11 gene may be involved in the carcinogenesis and development of GC and may provide useful information for the prediction of the malignant behaviors of GC. And the expression of HOXA11 is impaired by DNA methylation. However, repression of HOXA11 expression promoted BGC-823 cell proliferation.
authors: Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China ; Department of Biochemistry and Molecular Biology, Medical School of Henan University, Kaifeng 475004, Henan Province, China.
authors: Yinguo
authors: Y
authors: Bai
authors: Department of Biochemistry and Molecular Biology, Medical School of Henan University, Kaifeng 475004, Henan Province, China.
authors: Na
authors: N
authors: Fang
authors: Department of Biochemistry and Molecular Biology, Medical School of Henan University, Kaifeng 475004, Henan Province, China.
authors: Tingxun
authors: T
authors: Gu
authors: Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.
authors: Yuhua
authors: Y
authors: Kang
authors: Department of pathology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.
authors: Jiang
authors: J
authors: Wu
authors: Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.
authors: Desheng
authors: D
authors: Yang
authors: Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.
authors: Hui
authors: H
authors: Zhang
authors: Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.
authors: Zhimin
authors: Z
authors: Suo
authors: Department of Biochemistry and Molecular Biology, Medical School of Henan University, Kaifeng 475004, Henan Province, China.
authors: Shaoping
authors: S
authors: Ji
keywords: Expression; Gastric cancer; HOXA11 gene; Methylation