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

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.