title: Clinical significance of promoter region hypermethylation of microRNA-148a in gastrointestinal cancers.
abstract: BACKGROUND
  MicroRNAs are associated with tumor genesis and progression in various carcinomas. MicroRNA-148a (miR-148a) was reported to have low expression in gastrointestinal cancers, and might be regulated by promoter region DNA methylation.
  
  
  METHODS
  Bisulfite-modified sequencing was used to determine the promoter region DNA methylation status of human gastrointestinal cancer cell lines. Expression levels of miR-148a in cell lines treated with 5-aza-2'-deoxycytidine were determined by quantitative real-time polymerase chain reaction. Total DNA was extracted from the tissues of 64 patients with gastric cancer and 51 patients with colorectal cancer. Methylation status was determined by methylation-specific polymerase chain reaction. All statistical analyses were performed with SPSS 17.0 software.
  
  
  RESULTS
  The promoter regions of genes in human gastrointestinal cancer cell lines were all hypermethylated, except for HT-29, and the expression of miR-148a tended to be higher than in controls after treatment with 5-aza-2'-deoxycytidine. The methylation-specific polymerase chain reaction results showed that 56.25% of gastric cancer tissues and 19.61% of colorectal cancer tissues were hypermethylated. A strong correlation was found between the expression of miR-148a and the methylation status of promoter regions (P<0.001, chi-square test and Pearson's correlation). Furthermore, promoter region CpG site hypermethylation of miR-148a was correlated with increased tumor size (P=0.01) in gastric cancer after analyzing the correlation between methylation status and clinicopathologic characteristics.
  
  
  CONCLUSIONS
  The promoter region CpG sites were hypermethylated in gastrointestinal cancers. Promoter region hypermethylation status was associated with the expression of miR-148a and tumor invasiveness in gastric cancer, and may prove to be a new biomarker and method for treating gastric cancer.
authors.affiliation: Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Jingxu
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Yongxi
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Zhenning
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Guoli
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Xiaowan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Huimian
authors.initials: H
authors.lastname: Xu
keywords: CpG site; clinicopathologic characteristics; methylation; microRNAs