HCAR2 inhibits prostate cancer invasion and metastasis by regulating cAMP signaling pathway.

Abstract

Prostate cancer (PCa) is one of the most prevalent malignancies affecting men and a significant contributor to the rising global cancer-related mortality rate. Nevertheless, intricate processes underlying invasion and metastasis remain largely unclear. The objective of our research was to explore the function and underlying mechanisms of hydroxycarboxylic acid receptor 2 (HCAR2) in the invasion and metastasis of PCa. We analyzed differentially expressed genes in PCa through transcriptome sequencing. Then, we conducted bioinformatics analyses to investigate the correlation between HCAR2 and PCa. Furthermore, we overexpressed HCAR2 both in vitro and in vivo to investigate its role in regulating the proliferation and invasion of PCa cells as well as the tumorigenic ability of PCa cells. Finally, we treated PC3 cells with the signaling pathway inhibitor H89 on the basis of HCAR2 overexpression to explore the role of the cAMP signaling pathway in PCa. HCAR2 was significantly downregulated in PCa patients. HCAR2 had diagnostic significance for the survival prognosis of PCa patients, with a high diagnostic accuracy rate over a five-year period. The core targets of HCAR2 in PCa were involved in the cAMP signaling pathway. Furthermore, overexpression of HCAR2 repressed the proliferation, migration, and invasion abilities of PC3 and DU145 cells, as well as the tumorigenic ability of PCa cells in vivo. Finally, H89 treatment reversed the effects of HCAR2 overexpression on cAMP signaling pathway-related proteins, as well as on the proliferation, migration, and invasion abilities of PC3 cells. HCAR2 inhibited the proliferation and invasion of PCa cells through the cyclic adenosine monophosphate signaling pathway.