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

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.