A low level of GPR37 is associated with human hepatocellular carcinoma progression and poor patient survival

GPR37, also known as parkin-associated endothelin-like receptor (Pael-R), is an orphan G protein-coupled receptor (GPCR). It has been reported that GPCRs play vital roles in the development and progression of cancer. To investigate the potential roles of GPR37 in hepatocellular carcinoma (HCC), expression of GPR37 was examined in human HCC samples. Immunohistochemistry and Western blot analyses were performed for GPR37 in 57 hepatocellular carcinoma samples. GPR37 expression was low in hepatocellular carcinoma as compared with the adjacent non-tumorous tissues. Clinicopathological analysis showed that GPR37 expression was significantly correlated with histological grade and the level of alpha fetal protein (AFP) (P = 0.000 and 0.002, respectively). The Kaplan–Meier survival curves revealed that decreasing GPR37 expression was associated with poor prognosis in HCC patients, while in vitro, following the release from serum starvation of HuH7 HCC cell, the expression of GPR37 was downregulated. In addition, the transient GPR37 knockdown by siRNA in HuH7 cells significantly decreased the apoptosis of hepatoma cells with activation of the phosphatidylinositol 3-kinase-Akt signaling pathway. Our data suggest that GPR37 may play an important role in the pathogenesis of hepatocellular carcinoma by affecting the proliferation of H CC cells, and it could be a novel potential molecular therapy target for HCC.