Aflatoxin B(1) inhibits the type 1 interferon response pathway via STAT1 suggesting another mechanism of hepatocellular carcinoma

BACKGROUND: Aflatoxin B(1) (AFB(1)) contamination of food is very high in most sub-Saharan African countries. AFB(1) is known to cause hepatocellular carcinoma (HCC) by inducing mutation in the tumour suppressor gene TP53. The number of new HCC cases is high in West Africa with an accompanying high mortality. The type I interferon (IFN) pathway of the innate immune system limits viral infections and exerts its anti-cancer property by up-regulating tumour suppressor activities and pro-apoptotic pathways. Indeed, IFN-α is reported to show significant protective effects against hepatic fibrogenesis and carcinogenesis. However, the mechanism behind AFB(1) deregulation of the type I interferon (IFN) signalling pathway, with consequent HCC is largely unknown. This current study seeks to test the hypothesis that AFB(1) inhibits the type I IFN response by directly interfering with key signalling proteins and thus increase the risk of HCC in humans. METHODS: We evaluated the effects of AFB(1) on the type I IFN signalling pathway using IFN stimulated response element (ISRE)-based luciferase reporter gene assay. In addition, the effects of AFB(1) on the transcript levels of JAK1, STAT1 and OAS3 were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) and confirmed by immunoblot assay. RESULTS: Our results indicated that AFB(1) inhibited the type I IFN signalling pathway in human hepatoma cell line HepG2 cells by suppressing the transcript levels of JAK1, STAT1 and OAS3. AFB(1) also decreased the accumulation of STAT1 protein. CONCLUSION: The inhibition of the type I IFN anti-cancer response pathway by AFB(1) suggest a novel mechanism by which AFB(1) may induce hepatocellular carcinoma in humans.