The expression of Kelch-like protein 18 (KLHL18) in non-small cell lung cancer (NSCLC) is lower than that in normal lung tissue according to the Gene Expression Profiling Interactive Analysis database. KLHL18 is a BTB domain protein and binds cullin 3 (CUL3). However, whether this complex participates in ubiquitination-mediated protein degradation in NSCLC is unclear. Therefore, we aimed to investigate the role of KLHL18 in human NSCLC cells. We found that KLHL18 is downregulated in cancer cells and is associated with poor prognosis. Further, its expression was significantly associated with tumor node metastasis (TNM) stage, lymph node metastasis, and tumor size. In vitro analysis of NSCLC cells showed that overexpressing KLHL18 inhibited cell proliferation, migration, and invasion. We found that the tumor-inhibitory effect of the KLHL18 protein was achieved by promoting the ubiquitination and degradation of phosphatidylinositol 3-kinase (PI3K) p85α and inhibiting the expression of PD-L1 protein, ultimately preventing tumor cell immune escape. Our results identified the tumor-suppressive mechanism of KLHL18 and suggested that it is closely related to NSCLC occurrence and development. Further investigation of the underlying mechanism may provide new targets for NSCLC treatment.

中文翻译：

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KLHL18通过抑制PI3K / PD-L1轴活性来抑制非小细胞肺癌的增殖，迁移和侵袭

根据基因表达谱交互式分析数据库，非小细胞肺癌（NSCLC）中的Kelch样蛋白18（KLHL18）的表达低于正常肺组织中的表达。KLHL18是BTB结构域蛋白，结合culcul 3（CUL3）。但是，尚不清楚这种复合物是否参与泛素介导的NSCLC蛋白质降解。因此，我们旨在研究KLHL18在人类NSCLC细胞中的作用。我们发现KLHL18在癌细胞中下调，并与不良预后相关。此外，其表达与肿瘤结转移（TNM）阶段，淋巴结转移和肿瘤大小显着相关。对NSCLC细胞的体外分析表明，过量表达KLHL18会抑制细胞增殖，迁移和侵袭。我们发现，KLHL18蛋白的肿瘤抑制作用是通过促进磷脂酰肌醇3-激酶（PI3K）p85α的泛素化和降解并抑制PD-L1蛋白的表达来实现的，从而最终阻止了肿瘤细胞的免疫逃逸。我们的结果确定了KLHL18的肿瘤抑制机制，并暗示它与NSCLC的发生和发展密切相关。对潜在机制的进一步研究可能为NSCLC治疗提供新的靶标。