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Aflatoxin B1 downregulates ARID3 genes to overcome senescence for inducing hepatocellular carcinoma.

Authors :
Ara D
Dheeravath S
Mungamuri SK
Source :
Toxicon : official journal of the International Society on Toxinology [Toxicon] 2024 Nov 06; Vol. 250, pp. 108114. Date of Electronic Publication: 2024 Oct 02.
Publication Year :
2024

Abstract

Aflatoxins are major food contaminants, which cause hepatotoxicity, eventually leading to Hepatocellular carcinoma. Activated AFB1 forms adducts with DNA, which in turn activates checkpoint control. We show that AFB1 activates PI3K-Akt signaling, which is critical for cell survival. Simultaneous activation of both DNA checkpoint and proliferative signaling leads to Oncogene-Induced Senescence, a major tumorigenesis barrier. AFB1 downregulates ARID3A and ARID3B proteins to overcome this senescence program to induce hepatic tumors.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1879-3150
Volume :
250
Database :
MEDLINE
Journal :
Toxicon : official journal of the International Society on Toxinology
Publication Type :
Academic Journal
Accession number :
39366524
Full Text :
https://doi.org/10.1016/j.toxicon.2024.108114