A Systematic Study on the Anti-Tumor Effect of Combinatorial miRNA Expression in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer mortality worldwide. Treatment options for HCC patients are limited, especially for those with advanced HCC. Deregulation of microRNA (miRNA) expression is frequently observed in HCC, and many cellular targets of miRNAs are genetic regulators of tumorigenesis. In addition, miRNAs interact with each other to coordinate targeted gene expressions. The potential of devising combinatorial miRNA-based therapies for HCC, however, remains largely unexplored. Here, we performed high-throughput CombiGEM screens to characterize the anti-tumorigenic effect of combinatorial miRNA expression. We assembled a library of 1,849 pairwise combinations for 43 human miRNAs that are downregulated in HCC patients/cell lines, and identified four miRNA combinations that exert anti-proliferative effect in HCC cells both in vitro and in vivo. Further experiments are underway to validate and characterize the anti-tumor effect of these newly identified miRNA combinations in HCC.