The Role of Androgen Receptor and microRNA Interactions in Androgen-Dependent Diseases

Abstract

The androgen receptor (AR) is a member of the steroid hormone receptor family of nuclear transcription factors. It is present in the primary/secondary sexual organs, kidneys, skeletal muscles, adrenal glands, skin, nervous system, and breast. Abnormal AR functioning has been identified in numerous diseases, specifically in prostate cancer (PCa). Interestingly, recent studies have indicated a relationship between the AR and microRNA (miRNA) crosstalk and cancer progression. MiRNAs are small, endogenous, non-coding molecules that are involved in crucial cellular processes, such as proliferation, apoptosis, or differentiation. On the one hand, AR may be responsible for the downregulation or upregulation of specific miRNA, while on the other hand, AR is often a target of miRNAs due to their regulatory function on AR gene expression. A deeper understanding of the AR-miRNA interactions may contribute to the development of better diagnostic tools as well as to providing new therapeutic approaches. While most studies usually focus on the role of miRNAs and AR in PCa, in this review, we go beyond PCa and provide insight into the most recent discoveries about the interplay between AR and miRNAs, as well as about other AR-associated and AR-independent diseases.

Keywords: androgen receptor; breast cancer; cancer; microRNA; prostate cancer.

Figure 1

MicroRNA (miRNA) biosynthesis and functions. MiRNA gene is transcribed by polymerase II to primary RNA (pri-miRNA). The ribonuclease Drosha is involved in the process of changing pri-miRNA into pre-miRNA. Afterwards, pre-miRNA is transported via Exportin-5 from the nucleus to the cytoplasm. Dicer is an endonuclease that splits pre-miRNAs into short miRNA duplexes. The unknown helicase participates in the splitting of the miRNA duplexes. The mature miRNA binds to the Argonaute (Ago) protein, creating a complex that targets the 3′ UTR region of targeted mRNA. Illustration created using BioRender.com (access date: 28 December 2021).

Figure 2

Main mechanisms of AR regulation by miRNA (A) and miRNA regulation by AR (B). Illustration created using BioRender.com (access date: 28 December 2021).