Aim: Investigate the role of crosstalk between HBV mutaitons and AKT1 in HCC progression. Methods: 52 HBV associated HCC patients with better progression (HCCB, >3 years survival) and 7 3 with poor progression (HCCP, <3years survival) after partial liver resection were analysed, respectively. HBV CP mutations were detected in serum samples. Proliferation and apoptotic indices were determined by counting KI67-positive cells and apoptotic figures stained by using apoptosis kit, respectively, on 3000 hepatocytes in HCC tissues. The microvessel density (MVD) was assessed by using anti-PODXL1antibody. Expressions of cell cycle Ku-0059436 cost regulators (p21, p27,

and p57) and AKT1 as well as its downstream gene S phase kinase associated protein 2 (SKP2) were examined in both human HCC tissues and HBV expressing Huh7 cells. Effects of coactivation of AKT1 and HBV mutations on cell cycle progression and celluar growth were also analysed. Results: When compared to patients with HCCB, KI67-positive cells and MVD were significantly higher, while apoptotic index was significantly lower in HCCP. Decreased levels of cell cycle regulators, and increased levels of AKT1 and SKP2 were more profound in HCCP than that in HCCB. Higher incidence of HBV

CP mutations was significantly associated Rucaparib research buy with HCCP when compared to HCCB (77.5% for HCCP and 27% for HCCB, respectively, p<0.05). The level of AKT1 expression correlated with enhanced proliferation and MVD, as well as the prevalence of CP mutations, and was inversely correlated with apoptosis and survival in HCC patients. HBV with CP mutations accelerated cell cycle regulators protein degradation while wild type HBV had no effect

in Huh7 cells. These effects were accompanied by a profound increase in AKT1.Coexpression of AKT1 and HBV CP mutations resulted in a dramatic increase of SKP2 expression, which in turn accelerated cellular growth and cell cycle progression in hepatoma cells when compared with cells overexpresssing AKT1 or HBV CP mutant alone. Small interfering RNA knockdown of SKP2 abrogated the effect of CP mutations on levels of cell cycle regulators, decreased cell proliferation, and restored cell cycle next arrest.Conclusion:. Our data demonstrate the crosstalk between HBV CP mutations and AKT1 in promoting liver tumor progression, and suggest that AKT1/SKP2 signals may serve as a potential target for treamtment of HBV associated HCC. Disclosures: The following people have nothing to disclose: Yuehua Huang, Lin Gu, Xiaohui Huang Background and aim: The development of novel therapies for HBV infection requires new antivirals that target viral life cycle functions other than the viral polymerase. HBV Core protein (Cp) represents an attractive new therapeutic target. Cp capsid assembly is critical for viral RNA packaging, reverse transcription and intracellular trafficking.