Following benign proliferative changes to the ductal lumen,

atypical ductal hyperplasia (ADH), DCIS and IDC are more likely to occur[2]. Molecular signatures for development and progression of breast cancer are poorly established, due to limited data for early lesions. Classification systems based on histological features and proliferation rate are useful in patient NVP-BEZ235 ic50 management to some extent, and are used to assign DCIS a grade of low, intermediate or high. The distinction between low grade DCIS and ADH is somewhat subjective, as they maintain many molecular and genetic similarities. High grade DCIS is much more likely to progress to IDC and is associated with increased likelihood of recurrence[1]. Currently there is no way clinicians can predict if a DCIS lesion will progress to IDC, which would improve therapeutic management. DCIS treatment is able to prevent progression from early stage breast cancer, but therapeutic options are lacking. DCIS lesions are heterogeneous with treatment success varying for the different molecular subtypes. Lumpectomy and radiation therapy remain the standard of care in most cases of DCIS. Estrogen receptor positive DCIS patients benefit from Tamoxifen treatment, but

no molecularly targeted treatment is available for basal lesions[2]. In contrast to the shared genetic and epigenetic alterations of IDC and DCIS, mRNA/miRNA expression profiles are significantly altered. Deep sequencing of DCIS and IDC lesions has identified differential miRNA signatures that may be involved in the acquisition of an

invasive phenotype. miR-140-3p downregulation was observed for all investigated groups of IDC and DCIS patients, leading our lab to investigate potential tumor suppressive roles[3]. Here we will review the underlying mechanisms behind microRNA-140 dysregulation in breast cancer. We will discuss the role of cancer stem cells in the DCIS to IDC transition and the importance of microRNAs in regulating breast cancer stem cells. Briefly, we will discuss the emerging role of exosomal miRNAs as intercellular signaling molecules. Finally, we will discuss possible Anacetrapib therapeutic avenues for modulating miRNA signaling in breast cancer and highlight the potential for epigenetic therapies to activate tumor suppressor miRNAs. MICRORNA BIOGENESIS MiRNAs are short noncoding RNA molecules, approximately 22 nucleotides in length, which bind primarily to the 3’ untranslated region (UTR) of messenger RNAs. The primary function of miRNAs is to regulate gene expression. miRNAs function through targeting mRNA for degradation or translational inhibition. mRNA is targeted through a semi-complimentary seed sequence (6-9 bp) in miRNAs, which guides binding to the miRNA response elements. Each seed sequence potentially matches hundreds of mRNA molecules, giving the miRNA many potential targets[4].