Abstract
It is well established that somatic mutations and escape of immune disruption are two essential factors in cancer initiation and progression. With an increasing number of second-generation sequencing data, transcriptomic modifications, so called RNA mutations, are emerging as significant forces that drive the transition from normal cell to malignant tumor, as well as providing tumor diversity to escape an immune attack. Editing of adenosine to inosine (A-to-I) in double-stranded RNA, catalyzed by adenosine deaminases acting on RNA (ADARs), is one dynamic modification that in a combinatorial manner can give rise to a very diverse transcriptome. Since the cell interprets inosine as guanosine (G), A-to-I editing can result in non-synonymous codon changes in transcripts as well as yield alternative splicing, but also affect targeting and disrupt maturation of microRNAs. ADAR-mediated RNA editing is essential for survival in mammals, however, its dysregulation causes aberrant editing of its targets that may lead to cancer. ADAR1 is commonly overexpressed, for instance in breast, lung, liver and esophageal cancer as well as in chronic myelogenous leukemia, where it promotes cancer progression. It is well known that ADAR1 regulates type I interferon (IFN) and its induced gene signature, which are known to operate as a significant barrier to tumor formation and progression. Adding to the complexity, ADAR1 expression is also regulated by IFN. In this review, we discussed the regulatory mechanisms of ADAR1 during tumorigenesis through aberrant editing of specific substrates. Additionally, we hypothesized that elevated ADAR1 levels play a role in suppressing an innate immunity response in cancer cells.