Melanoma is an aggressive skin carcinoma with poor prognosis, and is prevalent worldwide. It was demonstrated that microRNA (miR)-21 and mitogen-activated protein kinase kinase 3 (MKK3) both participated in the occurrence and development of various tumors; however, their detailed roles in the progression of melanoma remain unclear. Reverse transcription-quantitative PCR (RT-qPCR) and western blot analyses were conducted to examine the expression levels of miR-21 and MKK3 in clinical specimens of patients with melanoma and melanoma cell lines. A dual-luciferase reporter assay was performed to verify the target interaction between miR-21 and MKK3. The mRNA and protein expressions of MKK3 were measured using RT-qPCR and western blot analysis, respectively, following transfection with miR-21 mimics and inhibitor. Subsequently, Cell Counting Kit-8 and colony formation assays, and flow cytometry were conducted to assess the effects of miR-21 and MKK3 on the cell growth of melanoma. Cell migration and invasion experiments were performed to evaluate the effects of miR-21 and MKK3 on the cell metastasis of melanoma. It was revealed that MKK3 was upregulated, and miR-21 was downregulated in patients with melanoma and melanoma cell lines. MKK3 was demonstrated to be a direct target of miR-21. Furthermore, it was demonstrated that upregulated miR-21 expression and downregulated MKK3 expression suppressed cell proliferation and colony formation, promoted apoptosis, delayed the cell cycle, and inhibited cell migration and invasion. The present findings suggested that miR-21 could inhibit the cell growth and metastasis of melanoma by negatively regulating MKK3.

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