Arid1a promotes tumor initiation but restrains progression and metastasis in liver cancer [ChIP-Seq]

ARID1A is hypothesized to be one of the most common tumor suppressors in human cancer. However, the functional consequences of ARID1A gain and loss are not clear. We report that mice with complete liver-specific Arid1a deficiency were resistant to MYC induced liver carcinogenesis, indicating a requirement during tumor initiation. Mechanistically, Arid1a loss constrained tumor formation by reducing Cytochrome P450 expression, which in turn mitigated oxidative stress. We also examined the heterozygous state and found it potentiated metastasis formation and heterozygous has similar gene accessibility pattern with homozygous compared to WT. Liver tumor tissues were collected from LAP-MYC; Arid1a WT,Arid1a Het and Arid1a Homo knockout mice, then fixed and genomic DNA were isolated. Analysis of genomic occupancy of c-MYC in the cells from LAP-MYC;Arid1a WT,Arid1a Het and Arid1a Homo liver tumors by Chip-seq.