Overexpression of the miR-17-92 polycistron promoted lymphomagenesis in c-myc transgenic mice. c-myc is overexpressed in HCC tumors and cell lines. We have used cloning and Northern blot approaches to analyze the expression of miR-17-92 in human liver and hepatoma cell lines. Cloning of miRNAs from HepG2, HepG2-2215, and PLC/PRF-5 hepatoma cell lines confirmed the increased frequency of the six miRNAs compared to liver. The cloning data were confirmed by Northern blot analysis for miR-17-5p, 18 and 92. The increased level of miR-92 correlated with increased steady state levels of c-myc protein in the different cell lines. Hepatocarcinogenesis in woodchuck hepatitis virus (WHV) carrier woodchucks is associated with activation of the N-myc2 gene by WHV DNA integration. We have surveyed 50 primary woodchuck HCCs from 22 WHV carrier woodchucks for miR-17-92 expression using Northern blots. We have detected high level expression of miR-92 in 100% of the HCCs compared to peritumor liver samples. We detected N-myc2 over-expression in 14 of 22 tumors suggesting that it may be a contributing factor to the over-expresion of miR-17-92. This is the first example of high penetrance over-expression of the oncogenic miR-17-92 polycistron in a primary hepatocellular carcinoma.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]