The Effect of Ibuprofen on Expression of Cox-1/2-Related miRNAs in MKN- 45 -Derived Cancer Stem-Like Cells

Context: ibuprofen is an anti-inflammatory drug that non-selectively blocks cyclooxygenases-1/2 (cox-1/2) enzymes and thus reduces the risk tumorigenesis. this study was designed to detect micrornas (mirnas) that target cox-1/2 mrna and to investigate the effect of ibuprofen on the expression of the mirnas in mkn-45-derived gastric cancer stem-like cells (cslcs). we were also aimed to find signaling pathways modulated by the mirnas. subjects and methods: the mirwalk database was used to recognize mirnas that targeted cox-1/2 genes. cslcs were derived from mkn-45 cell line and were then treated with ibuprofen. consequently, the effect of ibuprofen was evaluated on the expression of the mirnas by quantitative real-time polymerase chain reaction (qrt-pcr). finally, diana tools were used to identify signaling pathways that modulated by the mirnas. results: our bioinformatic investigation showed that hsa-mir-16-5p, hsa-mir-483- 5p, and hsa-mir-4669 targeted both cox-1 and cox-2 mrnas. the qrt-pcr results indicated that hsa-mir-16-5p and hsa-mir-4669 were overexpressed 2.34 and 9.47 folds, respectively, while hsamir- 483-5p under-expressed (2.08 folds) in ibuprofen-treated cslcs relative to untreated cells. moreover, it found that these mirnas are involved in pi3k-akt, p53, transforming growth factorbeta, phosphatidylinositol and insulin signaling pathways, cell cycle, extracellular matrix receptor interaction, gap junction, small cell lung cancer, prostate cancer, and chronic myeloid leukemia. conclusions: we suggest that ibuprofen may reduce the risk of gastric cancer by affecting the expression of mirnas that target cox-1/2. however, further research is necessary to unravel its exact effects.