Inactivation of miR-34a by aberrant CpG methylation in Kazakh patients with esophageal carcinomaReport as inadecuate

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Journal of Experimental and Clinical Cancer Research

, 33:20

First Online: 17 February 2014Received: 14 December 2013Accepted: 13 February 2014DOI: 10.1186-1756-9966-33-20

Cite this article as: Cui, X., Zhao, Z., Liu, D. et al. J Exp Clin Cancer Res 2014 33: 20. doi:10.1186-1756-9966-33-20


BackgroundEsophageal 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.

MethodsTo 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.

ResultsWe 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 expressionr = −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.

ConclusionsOur 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.

KeywordsMiR-34a Esophageal squamous cell carcinoma Kazakh Methylation Electronic supplementary materialThe online version of this article doi:10.1186-1756-9966-33-20 contains supplementary material, which is available to authorized users.

Xiaobin Cui, Zhimin Zhao contributed equally to this work.

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Author: Xiaobin Cui - Zhimin Zhao - Dong Liu - Tao Guo - Su Li - Jianming Hu - Chunxia Liu - Lan Yang - Yuwen Cao - Jinfang Jian


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