KLHL18 inhibits the proliferation, migration, and invasion of non-small cell lung cancer by inhibiting PI3K/PD-L1 axis activity.
KLHL18 inhibits the proliferation, migration, and invasion of non-small cell lung cancer by inhibiting PI3K/PD-L1 axis activity.
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KLHL 18通过抑制PI 3 K/PD-L1轴活性抑制非小细胞肺癌的增殖、迁移和侵袭。
DOI：
10.1186/s13578-020-00499-9
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发表时间：
2020-11-27
影响因子：
7.5
通讯作者：
Qiu X
中科院分区：
文献类型：
--
作者：
Jiang X;Xu Y;Ren H;Jiang J;Wudu M;Wang Q;Guan J;Su H;Zhang Y;Zhang B;Guo Y;Hu Y;Jiang L;Liu Z;Wang H;Cheng Y;Sun L;Qiu X
根据基因表达谱交互分析数据库，Kelch样蛋白18（KLHL 18）在非小细胞肺癌（NSCLC）中的表达低于正常肺组织。KLHL 18是BTB结构域蛋白，并结合cullin 3（CUL 3）。然而，这种复合物是否参与泛素化介导的蛋白质降解在NSCLC尚不清楚。因此，我们的目的是研究KLHL 18在人NSCLC细胞中的作用。我们发现KLHL 18在癌细胞中下调，并与预后不良相关。此外，它的表达与肿瘤淋巴结转移（TNM）阶段，淋巴结转移和肿瘤大小显著相关。NSCLC细胞的体外分析显示，过表达KLHL 18抑制细胞增殖、迁移和侵袭。我们发现KLHL 18蛋白的抑瘤作用是通过促进磷脂酰肌醇3-激酶（PI 3 K）p85α的泛素化和降解，抑制PD-L1蛋白的表达，最终阻止肿瘤细胞的免疫逃逸而实现的。本研究初步揭示了KLHL 18的抑瘤机制，提示其与NSCLC的发生发展密切相关。进一步研究其潜在机制可能为NSCLC治疗提供新的靶点。
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.
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DOI：
10.1186/s13046-018-0855-7
发表时间：
2018-08-13
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Jiang J;Xu Y;Ren H;Wudu M;Wang Q;Song X;Su H;Jiang X;Jiang L;Qiu X
通讯作者：
Qiu X
影响因子：
5.3
作者：
Melnick, A;Ahmad, KF;Licht, JD
通讯作者：
Licht, JD
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
13.8
作者：
Stogios, PJ;Privé, GG
通讯作者：
Privé, GG
影响因子：
64.5
作者：
Minor, DL;Lin, YF;Berger, JM
通讯作者：
Berger, JM