MicroRNAs as Regulators of Signal Transduction in Urological Tumors

Abstract

MicroRNAs (miRNAs) are short noncoding RNAs that have been shown to play pivotal roles in carcinogenesis. In the past decade, miRNAs have been the focus of much research in oncology, and there are great expectations for their utility as cancer biomarkers and therapeutic targets. In this review we examine how miRNAs can regulate signal transduction pathways in urological tumors. We performed in silico target prediction using TargetScan 5.1 to identify the signal transduction targets of miRNA, and we summarize the experimental evidence detailing miRNA regulation of pathways analyzed herein. miRNAs, which have been shown to be dysregulated in bladder, prostate, and renal cell cancer, are predicted to target key proteins in signal transduction. Because androgen receptor signaling is a major regulator of prostate cancer growth, its regulation by miRNAs has been well described. In addition, members of the phosphatidylinositol 3-kinase/Akt (RAC-alpha serine/threonine-protein kinase) signaling pathway have been shown to be susceptible to miRNA regulation. In contrast, there are very few studies on the impact of miRNA regulation on signaling by VHL (von Hippel-Lindau tumor suppressor) and vascular endothelial growth factor in renal cell carcinoma or by fibroblast growth factor receptor 3 and p53 in bladder cancer. Many miRNAs are predicted to target important signaling pathways in urological tumors and are dysregulated in their respective cancer types; a systematic overview of miRNA regulation of signal transduction in urological tumors is pending. The identification of these regulatory networks might lead to novel targeted cancer therapies. In general, the targeting of miRNAs is a valuable approach to cancer therapy, as has been shown recently for various types of cancer.