The roles of RNA editing in cancer immunity through interacting with interferon

Abstract

The interferon-activated tumor innate immunity can be primed by specific double-stranded RNA (dsRNA) sensors upon stimulation. A-to-I RNA editing in the dsRNA regions can have a potential function to regulate interferon-related cancer immunity. A systematical analysis of both the editing enzyme and specific enriched editing region in patients, tissues, and cell lines is performed to reveal the underlying mechanisms. We then validate the preferred editing of dsRNA regions, identify the hyper-editing in severe tumors, and discover the negative effect of editing on cancer immunity. Specifically, RNA editing acts as an inhibitor of PKR- and MDA5-related interferon pathways through the regulations of miRNAs and RNA-binding proteins and the deactivation of dsRNA sensors. With the alteration of interferons, subsequently, RNA editing represses the infiltration of CD8 and CD4 T cells and reduces the sensitivities of cancer drugs, such as cisplatin. These analyses on A-to-I RNA editing can improve the knowledge of tumorigenesis, immunology, and cancer-targeted immunotherapy. HighlightsO_LIThe preferred dsRNA region for RNA editing is validated. C_LIO_LIUpregulation of RNA editing in severe tumors is discovered. C_LIO_LIRNA editing inhibits PKR- and MDA5-related cancer immunity. C_LIO_LIRNA editing represses the infiltration of CD8 and CD4 T cells. C_LIO_LIRNA editing reduces the sensitivities of cancer drugs. C_LI