UC Davis

Prostate cancer (CaP) is the most frequently diagnosed malignant tumour and the second leading cause of cancer deaths in American men. One of the most troubling aspects of this disease is that, after androgen ablation therapy, androgen-dependent cancer cells inevitably progress to an androgen-independent status, for which no effective treatment has yet been developed. To date, the mechanisms that underlie the occurrence and progression of CaP remain largely unknown. Recent studies suggest that microRNAs (miRNAs) are involved in human tumourigenesis. Some aberrantly expressed miRNAs have been discovered in CaP cell lines, xenografts and clinical tissues and these CaP-related miRNAs may play critical roles in the pathogenesis of CaP. This review provides an overview of current findings about aberrantly expressed miRNAs in CaP. Although a number of CaP-related miRNAs were discovered, to date, only five are characterized for their functionalities: three as oncogenes and two as tumour suppressors. To understand the mechanisms of miRNA action as oncogenes or tumour suppressors, mRNA targets of miRNAs were characterized. Oncogenic miRNAs down-regulate the expression of apoptosis-related genes, and tumour suppressor miRNAs target the proliferation-related genes. Importantly, there is evidence that CaP-related miRNAs are regulated through androgen signalling and that this regulation may contribute to the development of androgen independence. Due to the oncogenic or tumour-suppressive properties of CaP-related miRNAs, they are highly likely to be of clinical use first as biomarkers but more importantly as therapeutic targets for prostate cancer treatment in the near future.