TY - JOUR
T1 - Transcriptional inhibiton of Hoxd4 expression by miRNA-10a in human breast cancer cells
AU - Tan, Yuliang
AU - Zhang, Bo
AU - Wu, Tao
AU - Skogerbø, Geir
AU - Zhu, Xiaopeng
AU - Guo, Xiangqian
AU - He, Shunmin
AU - Chen, Runsheng
N1 - Funding Information:
We thank Dr. Baochen Shi, Dr. Beibei Chen and Dr. Norman for useful discussions. This work was supported by a Natural Science Foundation of China grant (30630040), 973 (2007CB946901 & 2007CB935703) Projects from the Ministry of Science and Technology of China, and the Innovation Projects (KSCX2-YW-R-124) from Chinese Academy of Sciences.
PY - 2009/2/22
Y1 - 2009/2/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=65549158866&partnerID=8YFLogxK
U2 - 10.1186/1471-2199-10-12
DO - 10.1186/1471-2199-10-12
M3 - Article
C2 - 19232136
AN - SCOPUS:65549158866
SN - 1471-2199
VL - 10
JO - BMC Molecular Biology
JF - BMC Molecular Biology
M1 - 12
ER -