The role of miR‐17‐92 cluster in hepatic carcinogenesis

Abstract

MiR‐17‐92 cluster is a potent oncogenic miRNA which has been shown to promote cell proliferation, increase angiogenesis and sustain cell survival in several cancer types. However, the potential role of miR‐17‐92 cluster in hepatic carcinogenesis has not been investigated. This study was designed to examine the impact of miR‐17‐92 in hepatic cancer cells. qRT‐PCR analysis showed that the expression of miR‐17‐92 cluster is increased in several human hepatic cancer cell lines (Hep3B, Huh7 and HepG2) compared to the transformed, non‐cancerous hepatic cell line, THLE‐2. The miR‐17‐92 inhibitors (blocking the entire cluster or individual miRNAs within the cluster) prevented hepatic cancer cell growth. In contrast, stable transfection of pri‐miR‐17‐92 cluster increased tumor cell proliferation. Western blot analysis showed decreased PTEN protein in hepatic cancer cells transfected with the pri‐miR‐17‐92 cluster, suggesting that PTEN may represent one of the miR‐17‐92 downstream targets. Experiments are ongoing to document hepatocellular cancer development in transgenic mice with targeted expression of homo miR‐17‐92 cluster gene in the liver (driven by albumin‐cre, with or without diethylnitrosamine treatment). Results of these experiments are expected to provide important in vitro and in vivo evidences to define the role of miR‐17‐92 in hepatic carcinogenesis and tumor progression.