The increased risk of HCC in patients with hepatitis B virus or adeno-associated virus type 2 infection might involve activation of cyclin E1 and its effects on chromosomes and genomes of liver cells.
Ectopic BTG2 overexpression decreased HCC growth, caused cell cycle arrest at the G1 phase, and downregulated Cyclin D1 and Cyclin E1 protein expression.
The cyclin E1 gene represents the site of recurrent integration of the hepatitis B virus in the pathogenesis of hepatocellular carcinoma, and this event is associated with strong up-regulation of cyclin E1 expression.
In aged NEMO<sup>Δhepa</sup> mice, loss of CcnE1 resulted in significant reduction of liver tumorigenesis, while deletion of CcnE2 had no effect on HCC formation.
These findings indicate that miR-7 exerts tumor-suppressive effects in hepatocarcinogenesis through the suppression of oncogene CCNE1 expression and suggest a therapeutic application of miR-7 in HCC.
Our data provide novel mutual relationships amongst cyclin E1-E2-E2F1 and indicate their role in sustaining hepatocellular carcinoma cell proliferation/migration, validating the concept of an anti-cyclin E1-E2-E2F1 therapeutic approach for hepatocellular carcinoma.
We show that expression of new cyclin E1 mRNA variants IN3, Delta4, and Delta5 is associated with retarded proliferation in murine hepatocellular carcinoma.