Investigating the functional role of BUB1B in aflatoxin B1-associated hepatocarcinogenesis

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology Pub Date : 2025-03-25 DOI:10.1016/j.tox.2025.154127

Hayam Hamdy , Wafaa A. Aly , Eyad Elkord

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引用次数: 0

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, stemming from a complex interplay of genetic, environmental, and lifestyle factors. Aflatoxin B1 (AFB1), a prevalent food contaminant, is a known HCC risk factor, but its molecular mechanisms remain incompletely understood. This study investigated the contribution of BUB1B, a crucial spindle assembly checkpoint regulator, in AFB1-induced hepatocyte malignant transformation, we assessed AFB1's impact on cell proliferation, viability, cell cycle regulation, and BUB1B expression. BUB1B knockdown via siRNA revealed its role in epithelial-mesenchymal transition (EMT), cell motility, and proliferation. AFB1 exposure significantly altered cell proliferation and cell cycle dynamics, correlating with increased BUB1B expression. Furthermore, we identified a significant interaction between BUB1B and the IL12A-JAK2/STAT4 signaling pathway, suggesting a mechanism for immune evasion and tumor progression. These findings highlight BUB1B's critical role in AFB1-induced hepatocarcinogenesis and establish its potential target for HCC. Further research is needed to fully elucidate the underlying molecular mechanisms and explore the therapeutic implications of BUB1B inhibition in HCC treatment.

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来源期刊

Toxicology 医学-毒理学

CiteScore

7.80

自引率

4.40%

发文量

222

审稿时长

23 days

期刊介绍： Toxicology is an international, peer-reviewed journal that publishes only the highest quality original scientific research and critical reviews describing hypothesis-based investigations into mechanisms of toxicity associated with exposures to xenobiotic chemicals, particularly as it relates to human health. In this respect "mechanisms" is defined on both the macro (e.g. physiological, biological, kinetic, species, sex, etc.) and molecular (genomic, transcriptomic, metabolic, etc.) scale. Emphasis is placed on findings that identify novel hazards and that can be extrapolated to exposures and mechanisms that are relevant to estimating human risk. Toxicology also publishes brief communications, personal commentaries and opinion articles, as well as concise expert reviews on contemporary topics. All research and review articles published in Toxicology are subject to rigorous peer review. Authors are asked to contact the Editor-in-Chief prior to submitting review articles or commentaries for consideration for publication in Toxicology.