Objective: Skin cutaneous melanoma (SKCM) is a common cutaneous malignant tumour. This study explored the expression and the downstream regulation mechanism of guanylate binding protein 2 (GBP2), an interferon (IFN)-induced protein, in SKCM.

Methods: Western blot was employed to verify the expression of SBP2 and its downstream Wnt/β-catenin pathway-related proteins. We studied the relationship between GBP2 and the SKCM prognosis through database analysis. , gain-and-loss-of function experiments were conducted in SKCM cells. Cell viability was monitored by the cell counting kit-8 (CCK8) assay, the colony formation assay detected cell proliferation, and apoptosis was verified by flow cytometry. Transwell assay was conducted to test cell invasion and migration, while Western blot was employed to monitor the epithelial-mesenchymal transition (EMT) of SKCM cells.

Results: The GBP2 expression in SKCM cells and tissues was lower than normal cells and tissues. GBP2 overexpression inhibited SKCM cell proliferation, migration, invasion, and EMT and promoted cell apoptosis. In contrast, the GBP2 knockdown had the reverse effect. Mechanically, Wnt/β-catenin was inactivated by GBP2 overexpression and was enhanced by GBP2 knockdown. Drug activation of Wnt/β-catenin significantly attenuated the malignant phenotypic inhibition induced by GBP2 up-regulation in SKCM cells.

Conclusion: GBP2 exerts anti-tumour effects by inhibiting the Wnt/β-catenin pathway in SKCM and is related to a favourable prognosis.

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