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Gastric cancer (GC) poses a serious public health threat and the 5‑year survival rate of patients with GC is low. MicroRNAs (miRNAs/miRs) may serve oncogenic or tumor suppressor functions during tumorigenesis by regulating cell proliferation, apoptosis, migration and invasion and it has been demonstrated that they may be dysregulated in various types of cancer. The present study demonstrated that miR‑144 and GATA4 were downregulated in GC tissues and cell lines and suggested that this may be due to hypermethylation. Additionally, miR‑144 and GATA4 had synergistic effects on GC cells by repressing cell proliferation and inducing cell cycle arrest and apoptosis. The results of bioinformatics and a luciferase reporter assay indicated that cyclooxygenase‑2 (COX‑2) is a direct target of miR‑144 and that miR‑144 negatively regulated the expression of COX‑2, which inhibits the viability of GC cells. GATA4 also induced a similar effect on COX‑2. Taken together, the results of the present study may improve understanding of the underlying mechanism of miR‑144 and GATA4 in GC. [ABSTRACT FROM AUTHOR]