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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.

journal_name

J Exp Clin Cancer Res

journal_title

Journal of experimental & clinical cancer research : CR

authors

Cui X,Zhao Z,Liu D,Guo T,Li S,Hu J,Liu C,Yang L,Cao Y,Jiang J,Liang W,Liu W,Li S,Wang L,Wang L,Gu W,Wu C,Chen Y,Li F

doi

10.1186/1756-9966-33-20

subject

Has Abstract

pub_date

2014-02-17 00:00:00

pages

eissn

0392-9078

issn

1756-9966

pii

1756-9966-33-20

journal_volume

pub_type

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