Introduction: The abnormal expression of Zinc Finger Protein 750 (ZNF750) has been reported in neoplastic diseases. This study investigated the functional role of ZNF750 in the progression of melanoma.
Material and methods: Quantitative real-time PCR and immunohistochemistry (IHC) were performed to detect the expression levels of ZNF750 in patients diagnosed with primary cutaneous malignant melanoma. The correlation between clinical-pathological features and ZNF750 expression were clarified. Cell Counting Kit-8 (CCK-8), colony formation and transwell assays were used to explore the effects of ZNF750 on the proliferation, colony formation, migration and invasion of melanoma cells. Western blot assay was used to evaluate the effects of ZNF750 on regulating epithelial-mesenchymal transition (EMT) related proteins.
Results: ZNF750 expression was down-regulated in human melanoma tissues and cells, and correlated with the clinical-pathological features including tumor size, lymph node metastasis, and Clark classification in patients with melanoma. In addition, overexpression of ZNF750 decreased the proliferation, invasion and suppressed EMT of melanoma cells, whereas ZNF750 depletion showed the opposite effects. Importantly, mechanistic analyses implied that upregulation of ZNF750 inhibited the expression of b-catenin and the downstream targets (cyclin D1, c-Myc, Bcl-2, MMP2 and MMP9), indicating it could block the activation of Wnt/b-catenin pathway. Consistently, knockdown of ZNF750 led to the opposite results.
Conclusions: Together, ZNF750 serves as a tumor suppressor for the development and progression of melanoma through regulating the Wnt/b-catenin pathway. This study confirms the involvement of ZNF750 in melanoma progression and may provide a promising therapeutic target for the treatment of melanoma.
Keywords: A2058 cells; A375 cells; EMT markers; expression; invasion; melanoma; proliferation; zinc finger protein 750.