Fig. 4

Bioinformatics combined with in vitro experiments to determine the presence of JUP/AGR2/LYPD3 signaling in melanoma cells. A Pathway and disease analysis of LYPD3. B Boxplot showing the expression level of LYPD3 among different pathologic stages (stage T, N, M and Breslow depth). C, D OS (C) and DSS (D) analysis according to the expression level of the LYPD3 gene were performed using melanoma cases in the TCGA-SKCM cohort. E The gene–gene interaction network for LYPD3 and neighboring genes was analyzed using the GeneMANIA database. Each node represents a gene. The line color represents possible relationship between the respective genes. F Correlation between LYPD3 level and four physically interacting genes as analyzed in TCGA-SKCM. Spearman method was applied. G Heatmap showing the correlation between LYPD3 and ten catenins, and the Spearman correlation coefficients are provided on the right side of the graph. H, I The positive correlation among LYPD3, JUP, and AGR2 was stronger in C2 than in C1. J UMAP plot demonstrating the expression of AGR2 and JUP. Higher expression is indicated by a greener color. (K-L) Verification of AGR2 and LYPD3 expression by Western blotting assay in melanoma cells transfected with oe and sh-JUP. One-way ANOVA was applied. ns not significant, *P < 0.05, **P < 0.01, ***P < 0.001