Androgen receptor and miR-206 regulation in prostate cancer

Abstract

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.

MicroRNA miR-145-5p inhibits Phospholipase D 5 (PLD5) to downregulate cell proliferation and metastasis to mitigate prostate cancer

“…Several miRNAs, which can serve prognostic roles, have been reported to be associated with PCa. A recent study presented that miR-206 binds with the androgen receptor and regulate the hormones in both breast and prostate cancer [ 29 ]. While miR-186-5p was found to play an oncogenic role in PCa.…”

A Sex Perspective in Neurodegenerative Diseases: microRNAs as Possible Peripheral Biomarkers

“…In this review, we reported sex-specific differences of peripheral miRNA levels in some NDs. As an example, miR-206, which is underexpressed in males with FTD and overexpressed in males with ALS, is regulated by hormones [ 94 , 95 , 96 ]. MiR-132 was found to be a particularly expressed miRNA in the cerebellum of males [ 97 ], which might explain why Yang and co-authors found it to be more upregulated in plasma samples of male patients with PD.…”

MiR‐206 inhibits proliferation and migration of prostate cancer cells by targeting CXCL11

“…28 All these studies further suggest that miR-206 may act as a tumor suppressor in multiple cancers. Although multiple studies of the function of miR-206 in PCa have been described, [29][30][31] the molecular mechanisms related to miR-206, however, remain obscure but attractive.…”