Endogenous Prostacyclin Signaling Regulating MicroRNA Expression in Mammalian Cells

Abstract

Prostacyclin (PGI2), a key vascular protector and a representative of eicosanoids metabolized from endogenous arachidonic acid (AA), involved in regulating cellular microRNA expression was found. A primary cultured cell line derived from mouse adipose tissue containing the pathway enzymes to metabolize endogenous AA to diverse eicosanoids was transfected with a cDNA of an engineered hybrid synthases which integrated cyclooxygenase‐1 and PGI2 synthase (PGIS) triple catalytic functions. It successfully redirected the cells (PGI2‐cells) stably and dominantly metabolizing the endogenous AA to PGI2. By microarray analysis for 119 miRNAs, expression of miRNA‐711 and 466f‐3p in the PGI2‐cells was dramatically (approximately 15‐folds) upregulated and down regulated, respectively. The up‐ and down‐ regulated miRNAs expression in the PGI2‐cells were completely abolished by specifically inhibiting either the PGI2 signalings through the membrane receptor or the PPARγ pathway. This study provides the evidences that PGI2 could be involved in much broad pathophysiological processes including the controlling of apoptosis, vascular inflammation, atherosclerosis, cancer, implantation, and obesity through its action on up‐ and down‐regulation of the miRNA expressions. The study has created a new dimension to understand the diverse biological functions of eicosanoids derived from endogenous AA in general.