Influence of aspartyl-tRNA synthetase 2 on the proliferation and migration of lung adenocarcinoma cells
10.12354/j.issn.1000-8179.2024.20241170
- VernacularTitle:冬氨酰-tRNA合成酶2对肺腺癌细胞增殖和迁移的影响
- Author:
Luan YANCHAO
1
;
Liang CHAO
1
;
Han QINGSONG
1
;
Liu LIRU
1
Author Information
1. 河北省胸科医院胸外科,河北省肺癌防治研究中心,河北省肺病重点实验室 石家庄市050001
- Publication Type:Journal Article
- Keywords:
lung adenocarcinoma (LUAD);
immune microenvironment;
DARS2;
proliferation;
prognostic biomarker
- From:
Chinese Journal of Clinical Oncology
2024;51(21):1081-1091
- CountryChina
- Language:Chinese
-
Abstract:
Objective:Based on the analysis of The Cancer Genome Atlas (TCGA) database,the expression levels and clinical significance of aspartyl-tRNA synthetase 2 (DARS2) in lung adenocarcinoma (LUAD) tissues were assessed. This study also explored the influence of DARS2 on proliferation,migration,and invasion of LUAD cells. Methods:We analyzed the expression profiles of DARS2 mRNA in LUAD samples from both the TCGA and Gene Expression Omnibus (GEO) databases,evaluating the differences in DARS2 mRNA expression between LUAD and normal lung tissues,and its potential association with clinicopathological characteristics. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the level of DARS2 mRNA,while Western blot verified the protein expression. Immunohis-tochemistry was used to determine the tissue location and to provide a comprehensive evaluation of DARS2 expression in LUAD tissues and cell lines. Using siRNA technology to transfer DARS2 specific siRNA and its negative control plasmid into A549 and H1299 cells. Cell prolifera-tion were measured by CCK-8,plate cloning was used to verify proliferation ability,while scratch and Transwell assays were used to detect migration and invasion abilities. The biological function of DARS2 in LUAD was examined through GO function and KEGG pathway enrich-ment analysis. A single-sample gene set enrichment analysis (ssGSEA) was used to explore the relationship between the expression level of DARS2 and tumor immune infiltration. Results:Analysis of TCGA and GEO databases showed that DARS2 mRNA was highly expressed in LU-AD tissues compared to adjacent tissues (all P<0.01). The expression level of DARS2 was significantly correlated with the pathological stage,T stage,N stage,M stage,sex,and smoking status of LUAD patients with LUAD (all P<0.05). High DARS2 expression predicted poor patient pro-gnosis (P<0.05). DARS2 was also highly expressed in LUAD and LUAD tissues (all P<0.05). DARS2 knockdown significantly reduced the prolif-eration,migration,and invasion abilities of A549 and H1299 cells (all P<0.05). DARS2-related genes were enriched in the cell cycle and Myc/Foxm1 pathways,which regulate key biological processes,such as cell proliferation. The expression level of DARS2 was significantly pos-itively correlated with the degree of Th2 cell infiltration into LUAD tissues. In contrast,it was negatively correlated with the infiltration of B,T,CD8+T,mast,and cytotoxic cells (all P<0.05). Conclusions:High DARS2 expression in LUAD tissues and cells indicates poor patient prognosis. Knocking down DARS2 expression inhibited the proliferation,migration,and invasion of LUAD cells. Therefore,DARS2 may be a therapeutic target and prognostic biomarker for LUAD.
