Inhibition Of HBV Replication And Related Oncological Signal Transduction Pathways Study By Lentiviral MicroRNA-based RNAi

Hepetocellular carcinoma (HCC) is one of the rare human neoplasms associated with viral infections. Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma. Prolonged expression of the viral regulatory protein HBx and the large envelope protein (LHBs) may contribute in deregulating the cellular transcription program and proliferation control, and sensitize liver cells to carcinogenic factors. Delivering siRNA and inhibiting HBV could involve the use of the structure of pre-microRNAs (pre-miRNAs). A lentiviral microRNA-based RNAi system was developed to drive hepatitis B virus x antigen–specific short siRNA in HepG2.2.15 cells. HBsAg in the supernatant and intracellular were analyzed by ELISA and western blot. HBx mRNA levels and HBV DNA in the supernatant were analyzed by realtime PCR. HepG2.2.15 cells were injected subcutaneously into both flanks of BALB/c nu/nu male mice. The tumor sizes were measured once every 5-10 days after RNAi. Our findings thus indicate that lentiviral microRNA-based RNAi can specifically mediate the down-regulation of viral gene expression leading to a reduction in viron production. Lentiviral micro-RNA based RNAi may be useful for therapy in HBV and HCC. HBV plays an important role in tumorigenicity in HCC and triggers specific oncogenic pathways.