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

Cui, X and Zhao, Z and Liu, D and Guo, T and Li, S and Hu, J and Liu, C and Yang, L and Cao, Y and Jiang, J and Liang, W and Liu, W and Li, S and Wang, L and Wang, L and Gu, W and Wu, C and Chen, Y and Li, F (2014) Inactivation of miR-34a by aberrant CpG methylation in Kazakh patients with esophageal carcinoma. Journal of Experimental and Clinical Cancer Research, 33 (1).

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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. © 2014 Cui et al.; licensee BioMed Central Ltd.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
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, Ccarywu@pitt.eduCARYWU
Chen, Y
Li, F
Date: 17 February 2014
Date Type: Publication
Journal or Publication Title: Journal of Experimental and Clinical Cancer Research
Volume: 33
Number: 1
DOI or Unique Handle: 10.1186/1756-9966-33-20
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
Date Deposited: 02 Dec 2016 20:35
Last Modified: 02 Feb 2019 16:58


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