biostudies-literatureSong JNational Natural Science Foundation of China7096https://www.ebi.ac.uk/biostudies/studies/S-EPMC9675819biostudies-literatureUnknown13(1)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 prNature communicationsMutant RIG-I enhances cancer-related inflammation through activation of circRIG-I signaling.PMC9675819819915058202203282221003Yin YMa LTian WZhang XCao YZhao WLu DSong JDeng XZhao XfalseMutant RIG-I enhances cancer-related inflammation through activation of circRIG-I signaling.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 pr2022-01-01T00:00:00Z2022 Nov2026-05-27T19:10:59.698Z2025-02-19T03:23:18.239ZS-EPMC96758193640276910.1038/s41467-022-34885-3