The Low-abundance Expression Gene GPR26 Is Used As An Anti-oncogene For Liver Cancer

G-protein-coupled receptors(GPCRs/GPRs)are a group of membrane protein receptors,whose expression is distributed in every organ of the human body.They play an important physiological role in many diseases,including the metastasis and progression of cancer.GPCRs always have tissue specific expression and so many high abundance GPCRs were identified as the drug targets by obvious expression differences in cancer.However,the function of low abundance GPCRs in their related cancers has not been illuminated.Here,we identified a low abundance GPCR-GPR26.The expression of GPR26 was examined in both HCC patient tumor samples and adjacent samples in 33 hepatocellular carcinoma patients.It was shown that the low abundance GPR26 m RNA and protein expression were also down-regulated in tumor tissues.In vitro functional assays showed GPR26 suppressed HCC cell proliferation,apoptosis,migration and invasion through Gs pathway.In vivo assays in HCC-bearing nude mice exhibited good anti-tumor effect of GPR26.At the same time,we found that GPR26 had methylation in liver cancer cells,and its protein expression was related to the proteasome-ubiquitination degradation mechanism,which provided a good explanation for its low expression in liver.Our results identified the low abundance GPR26 as an anti-cancer gene and a novel potential drug target for hepatocellular carcinoma.To our knowledge,this study identified the first example that might represent a new group of low abundance GPCRs actually function in cancers or other diseases.