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  hsa‑ mir‑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  factor‑ beta, 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.