Post-transcriptional suppression of G protein-coupled receptor 15 (GPR15) by microRNA-1225 inhibits proliferation, migration, and invasion of human colorectal cancer cells

Abstract

The G protein-coupled receptors (GPRs) have been shown to regulate several cancer related processes. The aberrant expression of GPRs has been linked to the development of several cancers. The present study was designed to examine the expression and decipher the role of GPR15 in the development of human colorectal cancer. The results revealed GPR15 to be significantly (P < 0.05) upregulated in colorectal cancer cells. The silencing of GPR15 inhibited the growth of the colorectal cancer cells via induction of apoptosis. Induction of apoptosis in colorectal cancer cells was associated increase in Bax and decrease in Bcl-2 expression. The silencing of GPR-15 also caused a significant (P < 0.05) decline in the migration and invasion of the colorectal cancer cells. Bioinformatic analysis and luciferase assay revealed that the expression of GPR15 to be post-transcriptionally regulated by microRNA-1225 (miR-1225). The expression of miR-1225 was found to significantly (P < 0.05) downregulated in colorectal cancer cells and its overexpression caused suppression of GPR15 and inhibited the proliferation of the colorectal cancer cells. Nonetheless, overexpression of GPR15 could avoid the growth inhibitory effects of miR-1225. The results suggest that the GPR15/miR-1225 axis play an important role in the development of colon rectal cancer and exhibit therapeutic implications for its treatment.