MicroRNAs as novel targets in liver cancer: Facing the clinical challenge

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide with a rising incidence in the western world. HCCs are characterized by a phenotypic and molecular heterogeneity that limits therapeutic progress. MicroRNAs play a major role for the pathogenesis and progression of liver cancer. As an essential part of the RNA interference machinery, microRNAs contribute to the regulation of many pro-oncogenic processes in HCC, including proliferation, migration, and survival. Therefore, these epigenetically active small molecules advanced to attractive targets for both diagnosis and therapy of liver cancer. Here, we will try to delineate the role of microRNAs during liver development and disease with a particular focus on the development of HCC. We will further aim to dissect the importance of microRNAs for the regulation of key signaling pathways in liver cancer and discuss the impact of microRNAs for the plasticity and phenotypic characteristics of hepatoma cells as well as for putative liver cancer stem cells. Further, we will review progress in high-throughput technologies as novel tools to identify patterns of deregulated microRNAs for diagnostic and prognostic classification of HCCs and indicate their potential as therapeutic targets. Finally, we will indicate potential conceptual and technological challenges that hamper the progress of microRNA-based treatment strategies in liver cancer.