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Aflatoxin B1 inhibits the type 1 interferon response pathway via STAT1 suggesting another mechanism of hepatocellular carcinoma

Narkwa, Patrick W., Blackbourn, David and Mutocheluh, Mohamed (2017) Aflatoxin B1 inhibits the type 1 interferon response pathway via STAT1 suggesting another mechanism of hepatocellular carcinoma Infectious Agents and Cancer, 12 (17).

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Abstract

Background Aflatoxin B1 (AFB1) contamination of food is very high in most sub-Saharan African countries. AFB1 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 AFB1 deregulation of the type I interferon (IFN) signalling pathway, with consequent HCC is largely unknown. This current study seeks to test the hypothesis that AFB1 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 AFB1 on the type I IFN signalling pathway using IFN stimulated response element (ISRE)-based luciferase reporter gene assay. In addition, the effects of AFB1 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 AFB1 inhibited the type I IFN signalling pathway in human hepatoma cell line HepG2 cells by suppressing the transcript levels of JAK1, STAT1 and OAS3. AFB1 also decreased the accumulation of STAT1 protein.

Conclusion The inhibition of the type I IFN anti-cancer response pathway by AFB1 suggest a novel mechanism by which AFB1 may induce hepatocellular carcinoma in humans.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Narkwa, Patrick W.
Blackbourn, Davidd.blackbourn@surrey.ac.uk
Mutocheluh, Mohamed
Date : 20 March 2017
Identification Number : 10.1186/s13027-017-0127-8
Copyright Disclaimer : © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Uncontrolled Keywords : Aflatoxin B1; Hepatocellular carcinoma; STAT1; Type I interferon pathway; HepG2 cells; JAK1; ISRE
Depositing User : Clive Harris
Date Deposited : 30 Nov 2017 13:37
Last Modified : 15 Mar 2018 08:11
URI: http://epubs.surrey.ac.uk/id/eprint/845076

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