MicroRNAs and Breast Cancer

MicroRNAs are a class of small non-coding RNAs that are involved in the negative regulation of gene expression primarily through binding to the 3’untranslated region of their target mRNA. MicroRNAs have multiple mRNA targets, each of which can be regulated by multiple microRNAs making this a complex regulatory network. The identification of their importance in different types of cancer and validation of their role in many processes related to cancer progression led to their description as a novel class of oncogenes (or ‘oncomirs’) and tumor suppressors. As a result, a massive influx of related research articles has emerged. Understanding the role of microRNAs in normal breast and cancer development and progression is critical to fully comprehend this disease. Many insights have been gained to date and this review highlights those with well established roles in breast cancer, as well as providing a comprehensive depiction of the most recent research articles in the field of microRNAs and breast cancer. MICRORNAs: AN INTRODUCTION MicroRNAs (miRNAs) are endogenous 19-25 nucleotide RNAs that have recently emerged as a novel class of small, evolutionarily conserved gene regulatory molecules involved in many critical developmental and cellular functions [1]. miRNAs base-pair with target mRNA sequences primarily in their 3’ untranslated region (3’UTR). Through specific base pairing, miRNAs induce mRNA degradation, translational repression, or both depending upon the complementarity of the miRNA to its mRNA target. Each miRNA can target numerous (100-1000) mRNAs, often in combination with other miRNAs, therefore controlling complex regulatory networks. It is estimated that there are ~900 miRNAs in mammalian cells, and that at least 30% of all genes are regulated by miRNAs [2, 3]. Over 10,000 identified mature miRNAs exist in species ranging from plants to humans, suggesting that miRNAs are ancient players in gene regulation [4]. Their existence and conservation throughout species supports the concept that they perform critical functions in gene regulation [4]. Indeed, the conserved evolution of both miRNAs and transcription factors highlights their importance in and the complexity of gene regulation [5]. Although, the primary role for miRNAs is through base pairing in the 3’UTR of genes as described above, there is compelling evidence that miRNAs may also bind to regions in the coding sequence of genes (for a review [6]). In addition, there is evidence to suggest that miRNAs may lead to the activation of certain genes through binding to sequences in the 5’UTR of genes [7]. Cleary, the complexity of miRNA-mediated regulation is still not yet fully realized and we should anticipate many advances in this field in the not too distant future. *Address correspondence to this author at the Department of Pathology & Laboratory Medicine, Hollings Cancer Center, 86 Jonathan Lucas Street, Medical University of South Carolina, Charleston, SC 29425, USA; Tel: 843-792-7889; Fax: 843-792-3940; E-mail: [email protected] What makes miRNAs particularly important is their involvement in most, if not all, fundamental biological processes [8-10]. Mounting evidence indicates that miRNAs may also play a significant role in cellular transformation and carcinogenesis acting either as oncogenes or tumor suppressors [11-16]. Furthermore, specific miRNA signatures have been identified for both solid cancers and hematologic malignancies [17-20]. Intriguingly, mounting evidence suggest that the power of miRNAs lies in the ability to distinguish specific cancer subtypes based on their miRNA profile, including, and of direct relevance to the studies described herein, breast cancer [17, 21]. Nonetheless, the identification and validation of specific targets has been limited.