No conflicts of interest were declared.
SP1 mediates the link between methylation of the tumour suppressor miR-149 and outcome in colorectal cancer†
Version of Record online: 17 DEC 2012
Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 229, Issue 1, pages 12–24, January 2013
How to Cite
Wang, F., Ma, Y.-L., Zhang, P., Shen, T.-Y., Shi, C.-Z., Yang, Y.-Z., Moyer, M.-P., Zhang, H.-Z., Chen, H.-Q., Liang, Y. and Qin, H.-L. (2013), SP1 mediates the link between methylation of the tumour suppressor miR-149 and outcome in colorectal cancer. J. Pathol., 229: 12–24. doi: 10.1002/path.4078
- Issue online: 17 DEC 2012
- Version of Record online: 17 DEC 2012
- Accepted manuscript online: 20 JUL 2012 08:23AM EST
- Manuscript Accepted: 14 JUL 2012
- Manuscript Revised: 4 JUL 2012
- Manuscript Received: 4 JAN 2012
- epigenetic silencing;
- promoter methylation;
- overall survival
Although recent studies indicate that DNA methylation contributes to the down-regulation of microRNAs (miRNAs) in colorectal cancer (CRC), this field remains largely unexplored. To identify methylation-silenced miRNAs and clarify their role in CRC, we performed a microarray analysis and screened for miRNAs that were induced in CRC cells by 5-aza-2′-deoxycytidine treatment or by the knockdown of DNA methyltransferases. The DNA methylation status of the candidate miRNA was analysed by bisulphite sequencing PCR and methylation-specific PCR. We found that miRNA-149 (miR-149) was epigenetically silenced in CRC and down-regulation of miR-149 was associated with hypermethylation of the neighbouring CpG island (CGI). Quantitative RT-PCR analysis demonstrated that the miR-149 level was markedly reduced in 51.6% of the CRC tissues compared with matched non-cancerous tissues. In addition, low expression of miR-149 was associated with a greater depth of invasion (), lower 5-year survival rate (), and was found to be an independent prognostic factor for overall survival () in a multivariate analysis. Moreover, transfection of miR-149 inhibited cell growth and invasion of CRC cells in vitro. We also identified mRNA for Specificity Protein 1 (SP1, Sp1), a potential oncogenic protein, as a target of miR-149. Our data suggest that, as a methylation-sensitive miRNA, miR-149 may play an important role as a tumour suppressor in CRC, which has prognostic and therapeutic implications. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.