Mutant RIG-I enhances cancer-related inflammation through activation of circRIG-I signaling.

ABSTRACT: RIG-I/DDX58 plays a key role in host innate immunity. However, its therapeutic potential for inflammation-related cancers remains to be explored. Here we identify frameshift germline mutations of RIG-I occurring in patients with colon cancer. Accordingly, Rig-i^fs/fs mice bearing a frameshift mutant Rig-i exhibit increased susceptibility to colitis-related colon cancer as well as enhanced inflammatory response to chemical, virus or bacteria. In addition to interruption of Rig-i mRNA translation, the Rig-i mutation changes the secondary structure of Rig-i pre-mRNA and impairs its association with DHX9, consequently inducing a circular RNA generation from Rig-i transcript, thereby, designated as circRIG-I. CircRIG-I is frequently upregulated in colon cancers and its upregulation pr

SUBMITTER: Song J 

PROVIDER: S-EPMC9675819 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature