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Gene expression levels in Arid1a deficiency mice liver and their littermates

ABSTRACT: ARID1A encodes a subunit of chromatin remodeling SWI/SNF complexes and has recently been suggested to be a tumor suppressor gene based on its loss of function somatic mutations, which are frequently found in various human tumors, including hepatocellular carcinoma (HCC). However, the role and mechanism underlying ARID1A mutations in tumorigenesis remain unclear. Here we show that hepatocyte-specific Arid1a deficiency in mice results in steatohepatitis and HCC development, which are accompanied by increased DNA damage, hepatocyte death, mitochondrial damage, innate immune cell infiltration, and large-cell dysplasia, as well as proinflammatory cytokines, TNF-alpha and IL-6 production, and activation of the STAT3 and NF-kappaB pathways. Interestingly, we found that Arid1a ablation-mediated hepatocyte death and liver inflammation are dependent upon Tp53-Bax proapoptotic signaling. In the absence of Tp53, hepatocyte death, immune cell infiltration, and TNF-alpha and IL-6 production were significantly decreased. This study provides an alternative mechanism by which Arid1a deficiency or loss of function mutations contributes to tumorigenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE58964 | GEO | 2016/12/31

SECONDARY ACCESSION(S): PRJNA253997

REPOSITORIES: GEO

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