IDDF2023-ABS-0150 PRKAR2A interacts with EMSY to promote colitis-associated tumorigenesis

BackgroundIt has been reported that protein kinase cAMP-dependent type II regulatory subunit alpha (PRKAR2A) directly modulates some signaling pathways and is essential for colitis regulation, but its role in colitis-associated tumorigenesis remains to be investigated. The aim of this study is to investigate the function and underlying mechanisms of PRKAR2A in the formation of colitis-associated cancer (CAC).MethodsWe generated global Prkar2a knockout (Prkar2a -/-) mice and placed them on an azoxymethane (AOM)/dextran sodium sulfate (DSS) experimental CAC protocol. The biological function of PRKAR2A was investigated in vivo. PRKAR2A interacting protein was identified by co-immunoprecipitation (co-IP) and mass spectrometry. The downstream pathways regulated by PRKAR2A were identified by RNA-seq and Western Blot assays. γ-H2A.X foci detected by immunofluorescence were used to determine the extent of DNA damage and repair.ResultsKnockout of Prkar2a in mice significantly inhibited CAC formation. In response to AOM/DSS, Prkar2a -/- mice showed a decrease in intestinal injury and inflammatory tumorigenesis as assessed by colon length (P