Epigenetic Regulation of miRNAs in Breast Cancer Formation and Progression

Abstract

Breast cancer is a leading cause of cancer death among women. Breast cancers include diverse subtypes, complicated cellular and molecular characteristics, a large number of genetic alterations, and a broad range of clinical behaviors. Great advances in cellular and molecular biology have shed new light on the roles of various genes in the formation and progression of breast cancer. Whereas somatic and germline abnormalities occur in many of these genes during breast carcinogenesis, it has become clear that epigenetic abnormalities also contribute to breast cancer development. For example, hypermethylation of promoter DNA is a common mechanism for the downregulation and loss of function of tumor suppressor genes, and abnormalities in chromatin modification dysregulate both tumor suppressor genes and oncogenes during the development and progression of breast cancer. microRNAs (miRNAs), a class of small, highly conserved endogenous non-protein-coding RNAs, downregulate their target genes to impact multiple biological processes including tumorigenesis, and thus represent another mechanism of epigenetic regulation of genes. Interestingly, a number of miRNAs are commonly dysregulated in breast cancer by different mechanisms including epigenetic mechanisms such as promoter methylation and histone modification. Furthermore, abnormal expression of miRNAs can also modulate the epigenetic profiles of cells. This chapter will focus on the influence of epigenetic changes on the expression of miRNAs in breast cancer formation and progression. We will also review the epigenetic events that are regulated by miRNAs in breast cancer.