Characterization of microRNAs regulating cyclooxygenase-2 gene expression

Cyclooxygenase 2 (COX-2) is an enzyme for catalyzing the biosynthesis of prostanoids including prostaglandins and thromboxanes. In this study, miRNA-mediated regulation of COX-2 expression was investigated by employing 9 miRNAs (miR-26a, -101a, -143, -144, -145, -199a, -199a*, -542-3p, -543). Western blot analysis revealed that ectopic expression of miR-26a, -145, -199a, -542-3p, and -543 significantly reduced the level of COX-2 protein. The inhibitory effect of miR-143, -542-3p, and -543 on COX-2 expression appeared to be mediated via interaction with predicted binding sites in the 3'-untranslated region (3'-UTR) of COX-2 as revealed by luciferase reporter assay. In IL-1β-treated A549 cells, the production of prostaglandin E₂ (PGE₂) was significantly inhibited by miR-26a, -145, -199a, -542-3p, and -543. Together, our findings contribute to the understanding of post-transcriptional regulation of COX-2 and suggest an important role for miRNAs in COX-2 over-expression during inflammation and tumorigenesis.