The Bone Microenvironment Soil in Prostate Cancer Metastasis: An miRNA Approach

SIMPLE SUMMARY: Prostate cancer (PCa) is the second most incident cancer in men worldwide. Despite having high cure rates when locally confined, PCa has a high risk of mortality in advanced stages, owing to the few treatment options for the metastatic disease, which occurs mostly in bones. Tumor progression seems to be related to deregulation of microRNA (miRNA) expression. These small noncoding RNA molecules act as posttranscriptional regulators of gene expression in donor cells or distant sites (by exosome transportation), preparing the future metastatic niche. Identification of suitable miRNAs may assist in an early and less invasive diagnosis and drug therapy, positively impacting patient quality of life and improving our understanding of the molecular aspects of bone metastasis. ABSTRACT: Bone metastatic prostate cancer (PCa) is associated with a high risk of mortality. Changes in the expression pattern of miRNAs seem to be related to early aspects of prostate cancer, as well as its establishment and proliferation, including the necessary steps for metastasis. Here we compiled, for the first time, the important roles of miRNAs in the development, diagnosis, and treatment of bone metastasis, focusing on recent in vivo and in vitro studies. PCa exosomes are proven to promote metastasis-related events, such as osteoblast and osteoclast differentiation and proliferation. Aberrant miRNA expression in PCa may induce abnormal bone remodeling and support tumor development. Furthermore, miRNAs are capable of binding to multiple mRNA targets, a dynamic property that can be harnessed for the development of treatment tools, such as antagomiRs and miRNA mimics, which have emerged as promising candidates in PCa treatment. Finally, miRNAs may serve as noninvasive biomarkers, as they can be detected in tissue and bodily fluids, are highly stable, and show differential expression between nonmetastatic PCa and bone metastatic samples. Taken together, the findings underscore the importance of miRNA expression profiles and miRNA-based tools as rational technologies to increase the quality of life and longevity of patients.