Investigating the molecular mechanisms of ADAR1 in colon cancer

Abstract

ADAR1 (adenosine deaminase acting on RNA) binds to double-stranded RNA (dsRNA) and catalyzes the deamination of adenosine through RNA editing to generate inosine. ADAR1 is known to inhibit the IFN (type I interferon) response and restrict the interaction between ZBP1 and RIPK3, thus suppressing ZBP1-mediated necroptosis. However, its mechanism in colon cancer is not clearly understood. This study analyzed changes in IFN signaling and ZBP1-mediated necroptosis pathway in ADAR1-depleted colon cancer cells with inducible knockdown using the tet on shADAR1 system, to clarify how ADAR1 regulates IFN signaling and ZBP1-mediated necroptosis. However, in contrast to previous studies, these observations showed that ADAR1 knockdown in colon cancer cells did not lead to activation of IFN signaling and ZBP1-mediated necroptosis. Furthermore, it was noted that the activation of IFN signaling, and ZBP1-mediated necroptosis did not occur upon ADAR1 knockdown, even in the presence of IFN and CBL0137 treatment. Therefore, our results suggest that ADAR1 exists in colon cancer cells in a different pathway than the known type I IFN signaling pathway and ZBP1-mediated necroptosis through RNA editing.