title: Inactivation of miR-34a by aberrant CpG methylation in Kazakh patients with esophageal carcinoma.
abstract: BACKGROUND
  Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with dismal prognosis and high incidence and mortality in Kazakh population. MiR-34a, a direct p53 target gene, possesses tumor-suppressive properties as they mediate apoptosis, cell cycle arrest, and senescence. The reduced expression of miR-34a by methylation in various cancers has been reported.
  
  
  METHODS
  To determine whether aberrant miR-34a methylation occurs in esophageal cancer, the DNA methylation of 23 CpGs sites in the miR-34a promoter was quantitatively analyzed in relation to the translation initiation site by MALDI -TOF mass spectrometry in 59 ESCC tissues and 34 normal tissues from the Kazakh population. Real-time PCR was used to detect the inhibition of miR-34a expression levels and to evaluate their association with methylation.
  
  
  RESULTS
  We found that miR-34a is more frequently methylated in ESCC (0.133 ± 0.040) than in controls (0.066 ± 0.045, P < 0.01). A nearly two-fold increase in miR-34a expression for the hypomethylated promoter was found in normal esophageal tissues than ESCC with hypermethylation (P <0.0001), pointing to a negative relationship between miR-34a CpG sites methylation and expression(r = -0.594, P = 0.042). The hypermethylation of miR-34a CpG_8.9 was associated with the advanced UICC stage III/IV of the esophageal cancers, and the hypermethylation of CpG_8.9 and CpG_5 of miR-34a was significantly correlated with lymph node metastasis.
  
  
  CONCLUSIONS
  Our findings suggest that miR-34a is involved in the etiology of ESCC and that hypermethylated miR-34a is a potential biomarker for ESCC diagnosis and prognosis. Moreover, targeting miR-34a methylation by demethylating agents may offer a novel strategy for anticancer therapy of ESCC.
authors: Xiaobin
authors: X
authors: Cui
authors: Zhimin
authors: Z
authors: Zhao
authors: Dong
authors: D
authors: Liu
authors: Tao
authors: T
authors: Guo
authors: Su
authors: S
authors: Li
authors: Jianming
authors: J
authors: Hu
authors: Chunxia
authors: C
authors: Liu
authors: Lan
authors: L
authors: Yang
authors: Yuwen
authors: Y
authors: Cao
authors: Jinfang
authors: J
authors: Jiang
authors: Weihua
authors: W
authors: Liang
authors: Wei
authors: W
authors: Liu
authors: Shugang
authors: S
authors: Li
authors: Lianghai
authors: L
authors: Wang
authors: Lidong
authors: L
authors: Wang
authors: Wenyi
authors: W
authors: Gu
authors: Chuanyue
authors: C
authors: Wu
authors: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, North 4th Road, Shihezi, Xinjiang 832002, China. cyz0515@sina.com.
authors: Yunzhao
authors: Y
authors: Chen
authors: Feng
authors: F
authors: Li
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D056726:Genetic Association Studies; D006801:Humans; D007623:Kazakhstan; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011401:Promoter Regions, Genetic
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs