Breast cancer is the most frequent cancer and the leading cause of cancer-related deaths in women worldwide. We determined the expression of COX2, COX1, 15-HPGDH mRNA and miRNAs (miR-21, miR-155) in three estrogen positive human breast cancer cell lines (MCF-7, BT-474, ZR-75-1). According to the results of three independent experiments the amount of COX1 and COX2 mRNA was significantly higher in the ZR-75-1 than in MCF-7 and BT-474 cells. Levels of total 15-HPGDH; functional 15-HPGDH mRNA in BT-474 cell line were lower than in MCF-7 and ZR-75-1 ones. The synthesis of 15-HPGDH enzyme in BT-474 line was blocked at the nuclear immature pre-mRNA processing level. miR-155 expression level was significantly lower than miR-21 in breast cancer cell lines. Correlations between the dysregulation of miR-21, miR-155 and 15-HPGDH, COX-1, COX-2 mRNA were identified. Expression of miR-21 was high in MCF-7, ZR-75-1 and BT-474 cell lines. Our results show that miR-21 and miR-155 regulate activity of several genes in cancer cells, their effect on the individual genes was in some cases cumulative. Based on our results, we concluded that miR-21, miR-155 suppress the work of tumor suppressor gene 15-HPGDH and induce potential oncogene COX-2 that promotes cell malignancy and metastasis of breast cancer.