Inactivation of miR-34a by aberrant CpG methylation in Kazakh patients with esophageal carcinoma

Journal of Experimental & Clinical Cancer Research

Feng Li⁴  Yunzhao Chen⁵  Chuanyue Wu³  Wenyi Gu¹  Lidong Wang²  Lianghai Wang⁵  Shugang Li⁵  Wei Liu⁵  Weihua Liang⁵  Jinfang Jiang⁵  Yuwen Cao⁵  Lan Yang⁵  Chunxia Liu⁵  Jianming Hu⁵  Su Li⁵  Tao Guo⁵  Dong Liu⁵  Zhimin Zhao⁵  Xiaobin Cui⁴ 

[1] Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane QLD 4072, Australia;Henan Key Laboratory for Esophageal Cancer, Zhengzhou University School of Medicine, Zhengzhou, Henan 450001, China;Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USA;Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China;Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, North 4th Road, Shihezi, Xinjiang 832002, China

关键词: Methylation;    Kazakh;    Esophageal squamous cell carcinoma;    MiR-34a;   

Others  :  804398
DOI  :  10.1186/1756-9966-33-20

 received in 2013-12-14, accepted in 2014-02-13,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Cui et al.; licensee BioMed Central Ltd.

【 图 表 】

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