Transcriptional activation of microRNA-34a by NF-kappa B in human esophageal cancer cells

BMC Molecular Biology

Yun Bai¹  Xueqing Xu¹  Yan Wang¹  Min Song¹  Hui Meng¹  Xuedan Chen¹  Kai Wang¹  Juan Li¹ 

[1] Department of Medical Genetics, College of Basic Medicine, Third Military Medical University, Chongqing, People's Republic of China

关键词: gene expression regulation;    p53;    NF-kappa B;    miR-34a;   

Others  :  1103232
DOI  :  10.1186/1471-2199-13-4

 received in 2011-11-04, accepted in 2012-01-31,  发布年份 2012

【 摘 要 】

Background

miR-34a functions as an important tumor suppressor during the process of carcinogenesis. However, the mechanism of miR-34a dysregulation in human malignancies has not been well elucidated. Our study aimed to further investigate the regulation mechanism of miR-34a.

Results

We found that overexpression of NF-kappa B p65 subunit could increase miR-34a levels in EC109, an esophageal squamous cancer cell line, while ectopic expression of DN IkappaB leaded to a significant reduction of miR-34a expression. Bioinformatics analysis suggested three putative KB sites in promoter region of miR-34a gene. Mutation two of these KB sites impaired p65 induced miR-34a transcriptional activity. Chromatin immunoprecipitation and electrophoretic mobility shift assays both showed that NF-kappaB could specifically bind to the third KB site located in miR-34a promoter. In addition, we found that overexpression of NF-kappaB p65 could not successfully induce miR-34a expression in esophageal cancer cell lines with mutant p53 or decreased p53. Reporter assay further showed that NF-kappaB-induced miR-34a transcriptional activity was reduced by p53 impairment. Nevertheless, CHIP analysis suggested binding of NF-kappaB to miR-34a promoter was not affected in cells with mutant p53.

Conclusions

Our work indicates a novel mechanism of miR-34a regulation that NF-kappaB could elevate miR-34a expression levels through directly binding to its promoter. And wildtype p53 is responsible for NF-kappaB-mediated miR-34a transcriptional activity but not for NF-kappaB binding. These findings might be helpful in understanding miR-34a abnormality in human malignancies and open new perspectives for the roles of miR-34a and NF-kappaB in tumor progression.

【 授权许可】

   
2012 Li et al; licensee BioMed Central Ltd.

【 图 表 】

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