KLHL18 inhibits the proliferation, migration, and invasion of non-small cell lung cancer by inhibiting PI3K/PD-L1 axis a
- PDF / 7,804,034 Bytes
- 15 Pages / 595.276 x 790.866 pts Page_size
- 32 Downloads / 194 Views
Cell & Bioscience Open Access
RESEARCH
KLHL18 inhibits the proliferation, migration, and invasion of non‑small cell lung cancer by inhibiting PI3K/PD‑L1 axis activity Xizi Jiang1, Yitong XU1,6, Hongjiu Ren1,6, Jun Jiang2, Muli Wudu3, Qiongzi Wang1, Jingqian Guan1, Hongbo Su1,6, Yao Zhang1, Bo Zhang1, Yuanzi Guo1, Yujiao Hu1, Lihong Jiang4, Zongang Liu5, Huanxi Wang1, Yu Cheng1, Limei Sun1,6 and Xueshan Qiu1,6*
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: Non-small cell lung cancer, Kelch-like protein 18, Diagnosis, PD-L1 protein, Ubiquitination, PI3K/AKT/ mTOR pathway Background The incidence of lung cancer in China is increasing, leading to an enormous social and economic burden [1]. In the past few decades, non-small cell lung cancer (NSCLC) and small cell lung cancer have emerged as the most commonly used diagnostic terms for lung cancer [2–5]. In recent years, several oncogenic genes have been discovered, and studies on the effects of EGFR mutations, *Correspondence: [email protected] 1 Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China Full list of author information is available at the end of the article
ALK fusions, and inhibition of hTERT overexpression suggested that these are primary therapeutic targets for NSCLC [6–8]. However, the molecular mechanisms underlying lung tumorigenesis remain unclear, making it vital to identify new therapeutic targets to improve treatment strategies for patients with lung cancer. The phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway is thought to be important in carcinogenesis and plays a crucial role in many human tumors [9]. The PI3K/ AKT/mTOR pathway can also increase the expression of PD-L1 at the protein level by inhibiting auto
Data Loading...
