Emerging aspects of microRNA interaction with TMPRSS2-ERG and endocrine therapy.

ABSTRACT

Prostate cancer (PCa) is the most common malignancy detected in males and the second most common cause of cancer death in western countries. The development of the prostate gland, is finely regulated by androgens which modulate also its growth and function. Importantly, androgens exert a major role in PCa formation and progression and one of the hypothesized mechanism proposed has been linked to the chromosomal rearrangement of the androgen regulated gene TMPRSS2 with ERG. Androgens have been therefore used as main target for therapies in the past. However, despite the development of endocrine therapies (e.g. androgen ablation), when PCa progress, tumors become resistant to this therapeutic castration and patients develop incurable metastases. A strategy to better understand how patients respond to therapy, in order to achieve a better patient stratification, consists in monitoring the levels of small noncoding RNAs (microRNAs). microRNAs are a class of small molecules that regulate protein abundance and their application as biomarkers to monitor disease progression has been intensely studied in the last years. In this review, we highlight the interactions between microRNAs and endocrine-related aspects of PCa in tissues. We focus on the modulation of TMPRSS2-ERG and Glucocorticoid Receptor (GR) by microRNAs and detail the influence of steroidal hormonal therapies on microRNAs expression.