Gnai3, also known as Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3, is involved in multiple biological processes. It participates in signaling pathways, such as those related to cytokine regulation and G-protein-coupled receptor signaling, and is of great biological importance in processes like cell migration, inflammation, and tumorigenesis [4,2,1]. Genetic models, like Gnai3-iresGFP reporter mice, are useful tools for studying its expression patterns [3].

In mice, GNAI1 and GNAI3 double-knockout (DKO) mice showed more severe colitis and significantly more colonic tumors compared to control mice after treatment with dextran sulfate sodium (DSS) and azoxymethane (AOM). The increased tumor development was associated with activation of NF-κB and STAT3, increased levels of GNAI2, nitric oxide synthase 2, and IL6, and changes in immune cell populations. Blocking IL6 with an antibody reduced the expansion of myeloid-derived suppressor cells (MDSCs) and the number of tumors in DKO mice, indicating that GNAI3 suppresses DSS-plus-AOM-induced colon tumor development by blocking IL6 signaling and down-regulating GNAI2 expression [1]. In hepatocellular carcinoma (HCC) cells, GNAI3 inhibits cell migration and invasion, and its down-regulation, potentially caused by up-regulation of miR-222, promotes HCC cell migration and invasion [4]. In non-alcoholic fatty liver disease (NAFLD) models, GNAI3 knockout enhanced dysregulated hepatic lipid metabolism and liver damage in mice, and down-regulation of GNAI3 promoted cellular lipid accumulation in HepG2 cells, suggesting GNAI3 is involved in NAFLD development [5].

In conclusion, Gnai3 plays crucial roles in various biological processes and disease conditions. The use of gene knockout mouse models, such as in colitis-associated tumorigenesis and NAFLD studies, has revealed its functions in inhibiting tumor development and regulating lipid metabolism. Its down-regulation in certain cancers like HCC is associated with increased cell migration and invasion. Understanding Gnai3's functions provides insights into disease mechanisms and potential therapeutic targets.