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In the United States, prostate cancer is the second leading cause of cancer-related deaths among men with an approximately 220,000 patients diagnosed with the disease in 2015. Prostate cancer is a hormone-driven tumor, and a common therapy is androgen-deprivation therapy (ADT) that involves anti-androgen treatments and/or castration therapy. Understanding the molecular basis for androgen-independent tumors is crucial toward developing new therapies for these patients. Understanding how androgen receptor itself functions is an important step in elucidating this process. Androgen receptor (AR), NR3C4, is a nuclear hormone receptor and functions as a DNA-binding transcription factor that regulates the expression of protein-coding genes. Translocation of AR to improper gene promoter elements or DNA-binding sites can result in an alteration in gene expression and thus normal prostate function. Therefore, it is crucial to understand which AR-promoter interactions are drivers of disease, as compared to promiscuous or benign AR-binding interactions. While a large portion of our genome is considered a gene desert, it is now appreciated that these regions of the genome contain non-coding RNA genes such as microRNAs (miRNAs). These non-coding RNAs have enormous regulatory potential, as they post-transcriptionally regulate gene expression by binding to messenger RNAs (mRNAs) to promote degradation or intervention of translational processes. In this review, we focus specifically on the notion that mis-regulation of non-coding RNAs such as miRNAs by improper AR–DNA binding are an important component that promotes prostate cancer. We also highlight the role of miR-206 and the interaction of miR-206 and AR within this process, given this is a miRNA known to be regulated by hormones in both breast and prostate cancer. [ABSTRACT FROM PUBLISHER]

Triple negative breast cancer (TNBC) has been associated with the lack of three hormone receptors; estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). However, a host of other steroid hormone receptors such as vitamin D receptor (VDR) is present in TNBC, and the role of these hormone receptors in breast tumorigenesis is unclear. The levels of microRNAs (miRNAs) are also expressed differently than in normal mammary epithelial cells. miRNAs are regulatory RNAs involved in various cellular functions, mainly gene silencing. Here, we reviewed the literature surrounding miRNAs in breast cancer, and performedin silicoanalysis to determine whether there was a correlation between levels of VDR in relation to miRNAs important in breast cancer development and tumorigenesis. We identified three miRNAs of interest, specifically, miR-23, miR-124, and miR-125. Through this research we determined the possibility that these miRNAs play an important role in controlling VDR activity and by virtue the development of breast cancer. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is an aggressive subtype with no clinically proven biologically targeted treatment options. The molecular heterogeneity of TNBC and lack of high frequency drivermutations other than TP53 have hindered the development of new and effective therapies that significantly improve patient outcomes. miRNAs, global regulators of survival and proliferation pathways important in tumor development and maintenance, are becoming promising therapeutic agents. We performed miRNA-profiling studies in different TNBC subtypes to identify miRNAs that significantly contribute to disease progression. We found that miR-34a was lost in TNBC, specifically within mesenchymal and mesenchymal stem cell-like subtypes, whereas expression of miR-34a targets was significantly enriched. Furthermore, restoration of miR-34a in cell lines representing these subtypes inhibited proliferation and invasion, activated senescence, and promoted sensitivity to dasatinib by targeting the proto-oncogene c-SRC. Notably, SRC depletion in TNBC cell lines phenocopied the effects of miR-34a reintroduction, whereas SRC overexpression rescued the antitumorigenic properties mediated by miR-34a. miR-34a levels also increased when cells were treated with c-SRC inhibitors, suggesting a negative feedback exists between miR-34a and c-SRC. Moreover, miR-34a administration significantly delayed tumor growth of subcutaneously and orthotopically implanted tumors in nude mice, and was accompanied by c-SRC downregulation. Finally, we found that miR-34a and SRC levels were inversely correlated in human tumor specimens. Together, our results demonstrate that miR-34a exerts potent antitumorigenic effects in vitro and in vivo and suggests that miR-34a replacement therapy, which is currently being tested in human clinical trials, represents a promising therapeutic strategy for TNBC. [ABSTRACT FROM AUTHOR]

This report summarizes information presented at the 2015 Keystone Symposium on "MicroRNAs and Noncoding RNAs in Cancer." Nearly two decades after the discovery of the first miRNA, the role of noncoding RNAs in developmental processes and the mechanisms behind their dysregulation in cancer has been steadily elucidated. Excitingly, miRNAs have begun making their way into the clinic to combat diseases such as hepatitis C and various forms of cancer. Therefore, at this Keystone meeting, novel findings were presented that enhance our view on how small and long noncoding RNAs control developmental timing and oncogenic processes. Recurring themes included (i) how miRNAs can be differentially processed, degraded, and regulated by ribonucleoprotein complexes, (ii) how particular miRNA genetic networks that control developmental process, when disrupted, can result in cancer disease, (iii) the technologies available to therapeutically deliver RNA to combat diseases such as cancer, and (iv) the elucidation of the mechanism of actions for long noncoding RNAs, currently a poorly understood class of noncoding RNA. During the meeting, there was an emphasis on presenting unpublished findings, and the breadth of topics covered reflected how inescapable the influence of noncoding RNAs is in development and cancer. [ABSTRACT FROM AUTHOR]

The most common form of breast cancer, luminal A, is estrogen receptor α (ERα)-positive and epithelial, but nevertheless can metastasize. The process of epithelial–mesenchymal transition (EMT) is probably the first step in the metastasis of epithelial cancers. We discuss the characteristics of EMT, including factors that induce EMT, and the relationship of EMT to cancer stem cells (CSCs). Estrogen/ERα signaling maintains an epithelial phenotype and suppresses EMT. An overview of microRNAs in breast cancer is presented, including how microRNA biogenesis is altered in cancer and regulated by ERα. We also discuss the role of the miR-200 family in opposing EMT. Finally, we discuss specific microRNAs that target ERα and regulate EMT in breast cancer, and the role of these microRNAs in breast cancer progression. [ABSTRACT FROM AUTHOR]

Malignant neoplasms are consistently among the top four leading causes of death in all age groups in the United States, despite a concerted effort toward developing novel therapeutic approaches [1] . Our understanding of and therapeutic strategy for treating each of these neoplastic diseases have been improved through decades of research on the genetics, signaling pathways, and cellular biology that govern tumor cell initiation, progression and maintenance. Much of this work has concentrated on post-translational modifications and abnormalities at the DNA level, including point mutations, amplifications/deletions, and chromosomal translocations, and how these aberrant events affect the expression and function of protein-coding genes. Only recently has a novel class of conserved gene regulatory molecules been identified as a major contributor to malignant neoplastic disease. This review focuses on how these small non-coding RNA molecules, termed microRNAs (miRNAs), can function as oncogenes or tumor suppressors, and how the misexpression of miRNAs and dysregulation of factors that regulate miRNAs contribute to the tumorigenic process. Specific focus is given to more recently discovered regulatory mechanisms that go awry in cancer, and how these changes alter miRNA expression, processing, and function. [ABSTRACT FROM AUTHOR]