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

Cui, Xiaobin, Zhao, Zhimin, Liu, Dong, Guo, Tao, Li, Su, Hu, Jianming, Liu, Chunxia, Yang, Lan, Cao, Yuwen, Jiang, Jinfang, Liang, Weihua, Liu, Wei, Li, Shugang, Wang, Lianghai, Wang, Lidong, Gu, Wenyi, Wu, Chuanyue, Chen, Yunzhao and Li, Feng (2014) Inactivation of miR-34a by aberrant CpG methylation in Kazakh patients with esophageal carcinoma. Journal of Experimental and Clinical Cancer Research, 33 1: . doi:10.1186/1756-9966-33-20

Author Cui, Xiaobin
Zhao, Zhimin
Liu, Dong
Guo, Tao
Li, Su
Hu, Jianming
Liu, Chunxia
Yang, Lan
Cao, Yuwen
Jiang, Jinfang
Liang, Weihua
Liu, Wei
Li, Shugang
Wang, Lianghai
Wang, Lidong
Gu, Wenyi
Wu, Chuanyue
Chen, Yunzhao
Li, Feng
Title Inactivation of miR-34a by aberrant CpG methylation in Kazakh patients with esophageal carcinoma
Journal name Journal of Experimental and Clinical Cancer Research   Check publisher's open access policy
ISSN 1756-9966
Publication date 2014-02-17
Year available 2014
Sub-type Article (original research)
DOI 10.1186/1756-9966-33-20
Open Access Status DOI
Volume 33
Issue 1
Total pages 14
Place of publication London, United Kingdom
Publisher BioMed Central Ltd.
Language eng
Subject 1306 Cancer Research
2730 Oncology
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.
Keyword Esophageal squamous cell carcinoma
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 81160301
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Australian Institute for Bioengineering and Nanotechnology Publications
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