Therapeutically targeting microRNAs in liver cancer.

MicroRNAs are small non-coding RNAs that negatively regulate gene expression through binding on the 3' untranslated region (UTR) of genes. Although microRNAs constitute a small fraction of the human genome, multiple studies have indicated their involvement in the pathogenesis of different types of cancer. Hepatocellular carcinoma (liver) is one of the most aggressive types of cancer with very few therapeutic options. Several studies have revealed that microRNAs are deregulated during liver cancer development and affect central oncogenic and anti-apoptotic liver cancer signaling pathways. Furthermore, the expression levels of specific microRNAs have been identified to be correlated with clinicopathological parameters and treatment responses in liver cancer patients. Here, we review how different epidemiological and liver cancer risk factors, such as the hepatitis B and C viruses, deregulate microRNA-gene circuits in the liver, contributing to liver cancer development. Furthermore, we describe how the most frequently deregulated microRNAs identified in liver cancer patients control their down-stream signaling pathways in liver cancer cells. In addition, we provide examples of microRNAs or microRNA inhibitors that have been used as liver cancer therapeutics and describe novel delivery technologies that could be potentially used in order to optimize the delivery of microRNAs in the liver without having any toxicity or side effects in other major organs. Taken together, there is ample evidence suggesting the deregulation of microRNA-gene circuits in liver, promising that the development of microRNA-based therapeutics could be a clinically viable approach for liver cancer patients.