BZW2 promotes malignant progression in lung adenocarcinoma through enhancing the ubiquitination and degradation of GSK3

The role of Basic leucine zipper and W2 domains 2 (BZW2) in the advancement of different types of tumors is noteworthy, but its involvement and molecular mechanisms in lung adenocarcinoma (LUAD) remain uncertain. Through this investigation, it was found that the upregulation of BZW2 was observed in LUAD tissues, which was associated with an unfavorable prognosis for individuals diagnosed with LUAD, as indicated by data from Gene Expression Omnibus and The Cancer Genome Atlas databases. Based on the clinicopathologic characteristics of LUAD patients from the tissue microarray, both univariate and multivariate analyses indicated that BZW2 functioned as an independent prognostic factor for LUAD. In terms of mechanism, BZW2 interacted with glycogen synthase kinase-3 beta (GSK3 beta) and enhanced the ubiquitination-mediated degradation of GSK3 beta through slowing down of the dissociation of the ubiquitin ligase complex, which consists of GSK3 beta and TNF receptor-associated factor 6. Moreover, BZW2 stimulated Wnt/beta-catenin signaling pathway through GSK3 beta, thereby facilitating the advancement of LUAD. In conclusion, BZW2 was a significant promoter of LUAD. The research we conducted identified a promising diagnostic and therapeutic target for LUAD.