To investigate the molecular mechanism of SREBP-1c expression regulated by HCV core protein.

HepG2 cells were transfected with pcDNA3.1/myc-His(-)-Core(1b, 3a), and the mRNA and protein expression levels of SREBP-1c and Sirt1 were determined by real time PCR and Western blot 48 h post-transfection. pGL4.10-Sirt1 and pcDNA3.1/myc-His(-)-Core(1b, 3a) were co-transfected into HepG2 cells, the Sirt1 promoter activity was measured by Luciferase assay 24h post-transfection. pmirGLO-SREBP-1c-3'-UTR and pcDNA3.1/myc-His(-)-Core (3a) were co-transfected into HepG2 cells, and the relative luciferase activity of SREBP-1c-3'-UTR was measured by Luciferase assay 48h post-transfection.

HCV core proteins (1b, 3a) up-regulate the mRNA levels (1.358 times and 1.337 times respectively; P = 0.043, 0.008) and protein expression (1.608 times and 1.926 times respectively, P = 0.042, 0.008) of SREBP-1c. Both HCV core proteins of genotype 1b and 3a up-regulate the mRNA levels (1.566 times and 1.71 times respectively; P = 0.037, 0.006) and protein expression (1.436 times and 1.588 times respectively, P = 0.026, 0.009) of Sirt1. The Sirt1 promoter did not show significant transcriptional activity in the presence of HCV core proteins (1b, 3a). The relative luciferase activity of SREBP-1c-3'-UTR shown significant decrease in the presence of HCV core protein of genotype 3a (RQ = 0.667, P = 0.008).

HCV core proteins up-regulate the expression levels of SREBP-1c and Sirt1, which may be one of the pathogenesis of HCV related steatosis. MicroRNA also involved in the regulation of SEBP-1c by HCV core protein. Whether there are microRNAs contribute to the regulation of Sirt1 by HCV core protein still need to be investigated.