Hepatocarcinogenesis is a complex process that includes pronounced necroinflammation, unregulated hepatocyte damage, subsequent extensive
fibrosis, and
carcinogenesis. GPR110 was an adhesion
G protein-coupled receptor. Analysis of the expression pattern of Gpr110 in mice displayed that Gpr110 was expressed highly in liver, implicating the tissue compartments where Gpr110 could execute its functions, the role of Gpr110 in the physiological and pathological state of liver remains unclear. Based on a Gpr110 knockout mouse model, we evaluated the role of Gpr110 in hepatocarcinogenesis by using a
carbon tetrachloride (CCl4)-induced liver injury and
fibrosis model, as well as
diethylnitrosamine (DEN) plus CCl4-induced
liver cancer model. In this study, we found subdued chronic liver injury, reduced compensatory proliferation, lower
liver fibrosis, but enhanced
inflammation occurred in Gpr110-/- mice during CCl4 challenge. In addition, Gpr110-/- mice were resistant to liver
tumorigenesis induced by DEN plus CCl4 injection. Molecular mechanisms underlying these differences correlated with augmented activation of the IL-6/STAT3 pathway, which exerted hepatoprotective effects during liver damage,
fibrosis, and
oncogenesis in Gpr110-/- mice. Furthermore, pharmacological inhibition of the activation of the IL-6/STAT3 pathway enhanced hepatic
fibrosis and promoted DEN plus CCl4-induced
carcinogenesis in Gpr110-/- mice. In summary, absence of Gpr110 decelerates
liver fibrosis/
cirrhosis progressing into
tumorigenesis, due to strengthening activation of the IL-6/STAT3 pathway, leading to a weaker liver injury and
fibrosis microenvironment. It is indicated that targeting Gpr110 and activating the IL-6/STAT3 pathway may be considered to be preventive methods for some
cirrhosis transition.