ARID1A deficiency promotes pancreatic tumorigenesis by reducing KRAS-induced senescence (RNA-Seq II)

ARID1A is one of the most frequently mutated epigenetic regulators in a wide spectrum of cancers. In this study, we identified the anti-senescence effect of ARID1A deficiency in the progression of pancreatic intraepithelial neoplasia (PanIN) by profiling the transcriptome of individual PanINs in the mouse model. Interestingly, we found that ARID1A deficiency activates the transcription of Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), which play essential roles in attenuating the senescence by significantly reducing reactive oxygen species (ROS) induced by oncogenic KRAS. Our findings further suggest that ALDH could be considered as a potential adjuvant target for prevention and treatment of pancreatic cancer. We dissected and profiled the transcriptomes of 20 lesoins from 2 KC mice and 24 lesions from 2 AKC mice.