MicroRNAs in the Development and Progression of Kidney Cancer

Abstract

Renal cell carcinoma (RCC), a genetically and histopathologically heterogeneous disorder, is the most lethal of all genitourinary cancers and is generally refractory to current treatment regimens, including chemotherapy and radiation therapy. Targeted therapies against critical signaling pathways associated with RCC pathogenesis, such as von Hippel–Lindau (VHL) tumor suppressor, vascular endothelial growth factor (VEGF), and mammalian target of rapamycin (mTOR), have shown limited efficacy so far. Therefore, there has been much interest in identifying novel biomarkers for early diagnosis, risk assessment, and the design of novel therapeutic interventions for the disease. MicroRNAs (miRNAs) have been shown to be differentially expressed in RCC and play an important role in RCC pathogenesis. Studies have analyzed global miRNA expression profiles and the functional role of specific miRNAs in RCC. Here, we review our current understanding about the role of miRNAs in RCC by summarizing findings from various studies. Several miRNA-profiling studies have been conducted to identify specific miRNA signatures capable of distinguishing tumor from normal tissue, identifying RCC subtypes and the potential use of miRNAs in prognosis. Specific miRNAs have been found to be associated with key signaling pathways implicated in RCC pathogenesis (including pVHL-HIF, VEGF, mTOR signaling). Although current knowledge of the role of miRNAs in RCC pathogenesis is far from complete, key future challenges await in the use of miRNAs as novel biomarkers for improved diagnosis, prognosis, and the development of novel therapies for improved clinical management of the disease.