Androgen Receptor and mIR-206 Regulation in Prostate Cancer

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) which involves anti-androgen treatments and/or castration therapy. Understanding the molecular basis for androgen-independent tumors is crucial towards developing new therapies for these patients. Understanding how androgen receptor itself functions, is an important first 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 site 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 RNAs 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 play an important part in prostate cancer development. We also highlight the role of miR-206 in this process, and the interaction of miR-206 and AR, given this is a miRNA known to be regulated by hormones in both breast and prostate cancer.

Transcription. 2017 Jun 09 [Epub ahead of print]

Fu Yee Gua, Brian D Adams

a The RNA Institute, State University of New York - University at Albany , 1400 Washington Ave, Albany , NY 12222.