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miRNAGene Promoters Are Frequent Targets of Aberrant DNA Methylation inHuman Breast Cancer

Thearticle presents a comprehensive analysis of miRNAs and theircontributions in breast cancer. The article has described miRNAs ascrucial regulators of gene expression. miRNAs are often deregulatedin cancer. The deregulation process is enabled by an epigeneticmechanism referred to as the aberrant DNA methylation. The articlemade use of 5-methylcytosine immunoprecipitation method coupled tothe miRNA tiling microarray hybridization. The method helped theresearchers to evaluate comprehensively the DNA methylation of themiRNA gene promoters in the breast cancer (Vrba et al., 2013). Thedocument below analyzes the article in terms of the value of theconducted research and the presentation of the results.


Theresearch aimed at determining the DNA methylation status of the miRNApromoters in the cells of breast cancer. The entire analysis made useof 5-methylcytosine immunoprecipitation. The method was also linkedto custom tiling microarray hybridization. The method was formulatedin a way that it could be able to determine the methylation level invarious in vitro and in vivo representations of both the normal aswell as the diseased mammary cells. The miRNA promoters’hypermethylation was verified through the MassARRAY technology (Vrbaet al., 2013).


Theresearch revealed that most of the miRNA promoters that were analyzedwere hypermethylated in the breast cancer cell lines. The researchalso revealed that these promoters were targeted in the breast tumortissues. However, these promoters were found to less frequent. Withthe use of MassARRAY technology, the chosen miRNA promoters wereverified. The combination of the miRNA expression data together withthe MassARRAY DNA methylation data revealed that out of twelve casesof miRNA promoters’ hypermethylation, six were linked withsilencing of the miRNA expression. In the remaining six cases, theDNA methylation failed to correlate with the miRNA level (Vrba et al,2013).

Upto that far, the research method is satisfying. However, theresearchers failed to explain crucial details of their findings. Theyhave noted that six miRNA promoters were involved in miRNAexpression’s silencing while the other six did not correlate withthe miRNA level. The researchers would have indicated the possiblecauses why there erupted a difference in behavior between the twogroups of the miRNA promoters. The entire study revealed that theaberrant DNA methylation of the large proportion of the miRNA genesoften led to the silencing of the miRNA expression in the breastcancer. According to the study, miRNAs play a significant role inregulating as well as maintaining the cell identity.

Theresearchers, however, failed to explain how the miRNAs carry outtheir maintenance and regulation roles. The researchers’observations suggest that the miRNA expression’s deregulationbecause of the aberrant DNA methylation is related to the humanbreast carcinogenesis. Approximately one-third of the miRNA promotersactive in the normal mammary cells contains hypermethylated DNAregions in the cells of the of breast cancer. The proportion wasdetected to be higher than the way observed for the protein-codinggenes. The study reports the systematic identification of the miRNAgene promoters’ aberrant DNA methylation in the breast cancer. Theaberrant DNA methylation present in the breast cancer cell lines isdetectable in the vivo breast tumor tissues and, therefore, it mighthave some clinical relevance (Vrba et al, 2013).

Accordingto the study, the miRNA targets of the aberrant DNA methylation canbe used for diagnostic roles. The miRNA genes that were silenced bythe aberrant DNA methylation in breast cancer are the possibletargets for the epigenetic drugs. The research was well done, butthere are inconsistencies that are worth critiques. The researchersfailed to explain the reasons why the miRNA promoters tend to operatethe way they do. As far as all the other aspects are concerned, thearticle was well done.


Theresults presented by the researchers are remarkable. The results cutacross both sides in that the study reveals that miRNA has power topromote and also diagnosis of the breast cancer. To some extent theresults were expected. However, the researchers went a mile aheadbeyond many people’s expectations. The results are well analyzedand also coupled with statistics. The results were also expressed ina clear and understandable way by all.


Thearticle is well analyzed and offers a very crucial topic that is ofgreat necessity. Breast cancer has been on the rise in the worldtoday. The fact that the article analyzes breast cancer makes it avery important article. It offers the reader basic information of howmiRNAs promoters are related to the breast cancer. The article waswell written and well organized. However, the researchers shouldprovide a provision that would explain the meaning of the scientificterms used in the article. This would make it easier the readers whodo not have biological knowledge to understand the article’scontent and follow it through. In future, I would like to make anexpansion of this research and figure out whether miRNAs can be usedto the advantage of the cancer patients, for example, contribute tohealing of breast cancer.


VrbaL., Mun˜oz-Rodrı´guez J., Stampfer M. &amp Futscher B. (2013).miRNA Gene Promoters Are Frequent Targets of Aberrant DNA Methylationin HumanBreast Cancer.PLoSONE8(1): e54398. doi:10.1371/journal.pone.0054398