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Additionally, deletion of KDM2B reduced the xenograft volumes in nude mice. In conclusion, KDM2B induces the EZH2/PKMYT1/Wnt/β-catenin axis by inhibiting the let-7b-5p expression, which promotes NSCLC growth. More investigations are essential to determine the oncogenic role of KDM2B in NSCLC.Melanoma spheroid-loaded 3D skin models allow for the study of crucial tumor characteristics and factors at a superior level because the neoplastic cells are integrated into essential human skin components, permitting tumor-skin model communication.