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Gastric cancer (GC) is one of the most common and fatal types of cancers worldwide and the specific mechanism has not been completely elucidated. microRNA (miR)‑3664‑5P has rarely been studied and the aim of the present study was to assess an association between miR‑3664‑5P and GC. Differences in miR‑3664‑5P expression in 100 GC (0.1846±0.08276) and paired normal tissues (0.4382±0.1595) were detected using reverse transcription‑quantitative polymerase chain reaction assays (P&lt;0.001). 5‑Ethynyl‑2‑deoxyuridine, Cell Counting Kit‑8, transwell and flow cytometry assays were performed in vitro and the results were further verified using a mouse xenotransplantation and a lung metastasis model in vivo. miR‑3664‑5P was significantly downregulated in GC tissues when compared with normal tissues and positively associated with the prognosis of patients with GC (P&lt;0.001). Overexpression of miR‑3664‑5P suppressed and miR‑3664‑5P knockdown promoted the proliferation and metastasis of GC cells in vitro and in vivo. Following the application of bioinformatic algorithms and luciferase reporter assays, metadherin (MTDH) was confirmed as the target gene of miR‑3664‑5P. miR‑3664‑5P reduced MTDH expression and downregulated the nuclear factor (NF)‑κB signaling pathway. Rescue experiments demonstrated that suppression of MTDH restored the effect of miR‑3664‑5P inhibitors on GC cell lines. The results suggested that miR‑3664‑5P suppressed the proliferation and metastasis of GC cells by attenuating the NF‑κB signaling pathway via MTDH targeting. Consequently, miR‑3664‑5P may have potential to be an independent prognostic factor and biomarker in GC.

miR‑3664‑5P suppresses the proliferation and metastasis of gastric cancer by attenuating the NF‑κB signaling pathway through targeting MTDH