Department of Cardiovascular Thoracic Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Cardiovascular Thoracic Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
Gene. 2025 Jan 30;935:149055. doi: 10.1016/j.gene.2024.149055. Epub 2024 Oct 28.
Personalized targeted therapy has become an important strategy for cancer treatment owing to its remarkable therapeutic efficacy and safety. However, drug resistance remains the primary cause of treatment failure. Basic leucine zipper and W2 domain 2 (BZW2), which is aberrantly expressed in cancer, has been implicated in tumor progression and may serve as a new therapeutic target. Therefore, the role of BZW2 in non-small cell lung cancer (NSCLC) requires further investigation.
The expression and genetic alterations of BZW2 in pan-cancers were explored using The Cancer Genome Atlas (TCGA) PanCancer databases. The mRNA and protein levels of BZW2 in patients with NSCLC were verified in our cohort. Functional experiments including CCK8, colony formation, and transwell assays were performed to evaluate the impact of BZW2 on the proliferative, migratory, and invasive capacities of SK-MES-1 cells. Gene Set Enrichment Analysis was used to identify underlying biological processes and pathways. Single-cell RNA (scRNA) sequencing data were employed to investigate the tumor microenvironment of NSCLC and the co-expression of BZW2 and stemness-related genes.
Dysregulated BZW2 expression was observed in various malignant tumors. BZW2 expression was found to be significantly elevated in NSCLC. BZW2 depletion inhibited the growth, mobility, and invasive abilities of lung squamous cell carcinoma SK-MES-1 cells. BZW2 may be related to signaling pathways such as nucleotide excision repair, ubiquitin-mediated proteolysis, and the P53 signaling pathway. Biological processes, including translational initiation, tRNA processing, and RNA methylation, were observed to be enriched in the high-BZW2 group. Furthermore, there was a positive correlation between BZW2 and the m6A- and m5C-related genes. scRNA analysis revealed a co-expression relationship between BZW2 and stemness-related genes such as CD44, SOX9, and CD133.
Elevated BZW2 expression is associated with the proliferation, migration, and invasion of NSCLC, and BZW2 may be a potential therapeutic target for NSCLC.
由于其显著的治疗效果和安全性，个性化靶向治疗已成为癌症治疗的重要策略。然而，耐药性仍然是治疗失败的主要原因。基本亮氨酸拉链和 W2 结构域 2（BZW2）在癌症中异常表达，与肿瘤进展有关，可能成为新的治疗靶点。因此，BZW2 在非小细胞肺癌（NSCLC）中的作用需要进一步研究。
使用癌症基因组图谱（TCGA）泛癌数据库探讨 BZW2 在泛癌中的表达和遗传改变。在我们的队列中验证了 NSCLC 患者中 BZW2 的 mRNA 和蛋白水平。进行 CCK8、集落形成和 Transwell 测定等功能实验，以评估 BZW2 对 SK-MES-1 细胞增殖、迁移和侵袭能力的影响。使用基因集富集分析鉴定潜在的生物学过程和途径。单细胞 RNA（scRNA）测序数据用于研究 NSCLC 的肿瘤微环境以及 BZW2 和干性相关基因的共表达。
BZW2 的表达失调在各种恶性肿瘤中观察到。在 NSCLC 中发现 BZW2 的表达显著升高。BZW2 耗竭抑制肺鳞状细胞癌 SK-MES-1 细胞的生长、迁移和侵袭能力。BZW2 可能与核苷酸切除修复、泛素介导的蛋白水解和 P53 信号通路等信号通路有关。在高 BZW2 组中观察到包括翻译起始、tRNA 加工和 RNA 甲基化在内的生物学过程富集。此外，BZW2 与 m6A 和 m5C 相关基因之间存在正相关。scRNA 分析显示 BZW2 与 CD44、SOX9 和 CD133 等干性相关基因存在共表达关系。
BZW2 表达升高与 NSCLC 的增殖、迁移和侵袭有关，BZW2 可能是 NSCLC 的潜在治疗靶点。
