Email updates

Keep up to date with the latest news and content from BMC Molecular Biology and BioMed Central.

Open Access Highly Accessed Research article

Transcriptional inhibiton of Hoxd4 expression by miRNA-10a in human breast cancer cells

Yuliang Tan12, Bo Zhang12, Tao Wu12, Geir Skogerbø1, Xiaopeng Zhu1, Xiangqian Guo12, Shunmin He12 and Runsheng Chen1*

Author Affiliations

1 National laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, PR China

2 Graduate University of Chinese Academy of Sciences, Beijing, 100037, PR China

For all author emails, please log on.

BMC Molecular Biology 2009, 10:12  doi:10.1186/1471-2199-10-12

Published: 22 February 2009

Abstract

Background

Small noncoding RNAs (ncRNAs), including short interfering RNAs (siRNAs) and microRNAs (miRNAs), can silence genes at the transcriptional, post-transcriptional or translational level [1,2].

Results

Here, we show that microRNA-10a (miR-10a) targets a homologous DNA region in the promoter region of the hoxd4 gene and represses its expression at the transcriptional level. Mutational analysis of the miR-10a sequence revealed that the 3' end of the miRNA sequence is the most critical element for the silencing effect. MicroRNA-10a-induced transcriptional gene inhibition requires the presence of Dicer and Argonautes 1 and 3, and it is related to promoter associated noncoding RNAs. Bisulfite sequencing analysis showed that the reduced hoxd4 expression was accompanied by de novo DNA methylation at the hoxd4 promoter. We further demonstrated that trimethylation of histone 3 lysine 27 (H3K27me3) is involved in the miR-10a-induced hoxd4 transcriptional gene silence.

Conclusion

In conclusion, our results demonstrate that miR-10a can regulate human gene expression in a transcriptional manner, and indicate that endogenous small noncoding RNA-induced control of transcription may be a potential system for expressional regulation in human breast cancer cells.