NOP14 inhibits melanoma proliferation and metastasis by regulating Wnt/β-catenin signaling pathway

Abstract

Malignant melanoma is an aggressive skin cancer with a high mortality rate. Nucleolar protein 14 (NOP14) has been implicated in cancer development. However, the role of NOP14 in malignant melanoma progression remains largely unclear. In this study, we observed that malignant melanoma tissue showed NOP14 down-regulation compared to melanocytic nevi tissues. Moreover, we observed that NOP14 expression was significantly associated with melanoma tumor thickness and lymph node metastasis. NOP14 overexpression in melanoma cells suppressed proliferation, caused G1 phase arrest, promoted apoptosis, and inhibited melanoma cell migration and invasion. Further investigations revealed that NOP14 overexpression reduced the expression levels of Wnt3a, β-catenin, and GSK-3β of the Wnt/β-catenin pathway. In summary, we demonstrated that NOP14 inhibited melanoma cell proliferation and metastasis by regulating the Wnt/β-catenin signaling pathway.

Figure 1.. Expression level of nucleolar protein 14 (NOP14) in malignant melanoma tissues and melanocytic nevi tissues. Scale bar: 50 μm.

Figure 2.. Effect of nucleolar protein 14 (NOP14) overexpression on melanoma cell proliferation. NOP14 mRNA levels (A) and protein levels (B) in melanoma cell lines transfected with NOP14 overexpression and empty vectors. C and D, Cell proliferation analysis of melanoma cells after transfection of NOP14 overexpression and empty vectors. Data are reported as means±SD. **P<0.01 vs empty vector (ANOVA).

Figure 3.. Apoptosis and cell cycle analysis of melanoma cells transfected with nucleolar protein 14 (NOP14) overexpression or empty vector. A and B, Apoptosis analysis of melanoma cells. C and D, Cell cycle analysis of melanoma cells. Data are reported as means±SD. **P<0.01 vs empty vector (t-test).

Figure 4.. Migratory ability and invasiveness of melanoma cells determined by transwell assay. NOP14: nucleolar protein 14. Scale bar: 50 μm. Data are reported as means±SD. **P<0.01 vs empty vector (t-test).

Figure 5.. Expression level of Wnt3a, β-catenin, and GSK-3β in melanoma cells. A to C, Relative expression and D, protein levels of Wnt3a, β-catenin, and GSK-3β in melanoma cells transfected with nucleolar protein 14 (NOP14) overexpression and empty vectors. Data are reported as means±SD. *P<0.05, **P<0.01 vs empty vector (ANOVA).