Jin Kai, Li Yongmeng, Wei Ruyuan, Liu Yanfei, Wang Shuai, Tian Hui
Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Department of Thoracic Surgery, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.
Cell Death Discov. 2024 Feb 29;10(1):105. doi: 10.1038/s41420-024-01879-7.
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 (GSK3β) and enhanced the ubiquitination-mediated degradation of GSK3β through slowing down of the dissociation of the ubiquitin ligase complex, which consists of GSK3β and TNF receptor-associated factor 6. Moreover, BZW2 stimulated Wnt/β-catenin signaling pathway through GSK3β, 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.
碱性亮氨酸拉链和W2结构域2（BZW2）在不同类型肿瘤进展中的作用值得关注，但其在肺腺癌（LUAD）中的参与情况和分子机制仍不明确。通过本研究发现，在LUAD组织中观察到BZW2上调，基因表达综合数据库和癌症基因组图谱数据库的数据表明，这与LUAD诊断患者的不良预后相关。基于组织芯片中LUAD患者的临床病理特征，单因素和多因素分析均表明BZW2是LUAD的独立预后因素。在机制方面，BZW2与糖原合酶激酶-3β（GSK3β）相互作用，并通过减缓由GSK3β和肿瘤坏死因子受体相关因子6组成的泛素连接酶复合物的解离，增强GSK3β的泛素化介导降解。此外，BZW2通过GSK3β刺激Wnt/β-连环蛋白信号通路，从而促进LUAD的进展。总之，BZW2是LUAD的重要促进因子。我们进行的研究确定了一个有前景的LUAD诊断和治疗靶点。
