2. Academic Validation
  3. 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

  • Cell Biosci. 2020 Nov 27;10(1):139. doi: 10.1186/s13578-020-00499-9.
Xizi Jiang 1,  Yitong Xu 1 2,  Hongjiu Ren 1 2,  Jun Jiang 3,  Muli Wudu 4,  Qiongzi Wang 1,  Jingqian Guan 1,  Hongbo Su 1 2,  Yao Zhang 1,  Bo Zhang 1,  Yuanzi Guo 1,  Yujiao Hu 1,  Lihong Jiang 5,  Zongang Liu 6,  Huanxi Wang 1,  Yu Cheng 1,  Limei Sun 1 2,  Xueshan Qiu 7 8
Affiliations

Affiliations

  • 1 Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
  • 2 Department of Pathology, The First Hospital of China Medical University, No. 155 NanjingBei Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China.
  • 3 Department of Pathology, The First Bethune Hospital of Jilin University, Changchun, Jilin, China.
  • 4 Department of Pathology, Basic Medical Sciences, Xinjiang Medical University, Urumqi, China.
  • 5 Department of Pathology, Chang'an District Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, No. 120 Wenyuan Middle Road, Guodu Street, Chang'an District, Xi'an, 710100, Shaanxi, China.
  • 6 Shengjing Hospital Affiliated With China Medical University, 19F, Building No. 1B, No. 36, Sanhao Street, Heping District, Shenyang, 110000, Liaoning, China.
  • 7 Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China. [email protected].
  • 8 Department of Pathology, The First Hospital of China Medical University, No. 155 NanjingBei Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China. [email protected].
PMID: 33292627 DOI: 10.1186/s13578-020-00499-9
Abstract

Background: 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.

Results: 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.

Conclusions: 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.

Keywords

Diagnosis; Kelch-like protein 18; Non-small cell lung cancer; PD-L1 protein; PI3K/AKT/mTOR pathway; Ubiquitination.

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