title: MicroRNA-219-2-3p functions as a tumor suppressor in gastric cancer and is regulated by DNA methylation.
abstract: OBJECTIVE
  Gastric cancer is the most frequent gastrointestinal tumor in adults and is the most lethal form of human cancer. Despite of the improvements in treatments, the underlying mechanism of gastric carcinogenesis is not well known. To define novel modulators that regulate susceptibility to tumorgenesis, we focused on miR-219-2-3p.
  
  
  METHODS
  Quantitative RT-PCR was employed to investigate the level of miR-219-2-3p in gastric cancer (GC) tissues (n = 113) and their matched adjacent normal tissues (n = 113). In vitro cell proliferation, apoptosis assays, cell migration, and invasion assays were performed to elucidate biological effects of miR-219-2-3p. Since silencing of miRNA by promoter CpG island methylation may be an important mechanism in tumorgenesis, GC cells were treated with 5-aza-2'-deoxycytidine and trichostatin A, and expression changes of miR-219-2-3p were subsequently examined by quantitative RT-PCR. Finally, the methylation status of CpG island upstream of miR-219-2-3p was analyzed by methylation-specific PCR in GC tissues (n = 22).
  
  
  RESULTS
  miR-219-2-3p was down-regulated in GC and cell lines. In addition, the experiments documented the lower expression of miR-219-2-3p in GC specimens with higher grade and later stage tumors. Meanwhile, miR-219-2-3p exerted antiproliferative, proapoptotic, and antimetastatic roles and reduced levels of p-ERK1/2 in GC cells. Furthermore, 5-aza-2'-deoxycytidine and trichostatin A increased the expression (~2 fold) of miR-219-2-3p in GC cells. By methylation-specific PCR, DNA methylation in the upstream region of miR-219-2-3p was detected in both adjacent normal tissues and cancer tissues. As expected, the methylation level was considerably higher in the miR-219-2-3p down-regulated group than up-regulated group.
  
  
  CONCLUSIONS
  miR-219-2-3p is potentially involved in gastric cancer progression and metastasis by regulating ERK1/2-related signal pathways, which may provide a novel therapeutic strategy for treatment of gastric cancer. Methylation mechanism may be involved in modulating the expression level of miR-219-2-3p in gastric cancer.
authors: Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China.
authors: Huizi
authors: H
authors: Lei
authors: Dongling
authors: D
authors: Zou
authors: Zheng
authors: Z
authors: Li
authors: Min
authors: M
authors: Luo
authors: Lei
authors: L
authors: Dong
authors: Bin
authors: B
authors: Wang
authors: Haixin
authors: H
authors: Yin
authors: Yanni
authors: Y
authors: Ma
authors: Changzheng
authors: C
authors: Liu
authors: Fang
authors: F
authors: Wang
authors: Junwu
authors: J
authors: Zhang
authors: Jia
authors: J
authors: Yu
authors: Yu
authors: Y
authors: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D019295:Computational Biology; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: C578248:MIRN219 microRNA, human; D035683:MicroRNAs
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