Expression and function of G protein-coupled receptor 37 in hepatocellular carcinoma

G protein-coupled receptors (GPRs) play a critical role in different types of cancer, including hepatocellular carcinoma (HCC). GPR37 is an orphan receptor associated with the development and progression of some types of cancer, but its role in liver disease and liver cancer is unknown. The aim of this project was to analyze the expression and function of GPR37 in HCC.

GPR37 expression was significantly higher in human HCC tissues than in corresponding non-tumorous liver tissues. In addition, in silico analyses showed that increased GPR37 expression in HCC correlated with poor progression-free and overall survival. Expression of GPR37 was also significantly higher in different human HCC cells compared to primary human hepatocytes at the RNA and protein level as analyzed by RT-qPCR and Western blotting. To get insight into the functional role of GPR37 in HCC, GPR37 was suppressed in HCC cells using RNAi technology. GPR37-suppressed HCC cells exhibited reduced proliferation and spheroid formation. Moreover, GPR37 suppression led to reduced activation of protumorigenic signaling pathways and reduced proinflammatory gene expression in HCC cells.

Our data indicate that GPR37 acts as a protumorigenic factor in HCC. Further studies are required to identify the ligand(s) that act via this G protein-coupled receptor on HCC cells and to assess the potential of GPR37 as a prognostic marker and therapeutic target in HCC.

Publication History

Article published online:
20 January 2025