miR-218-5p Targeting TPX2 Regulates p53 Pathway and Inhibits Malignant Progression of Lung Adenocarcinoma.
10.3779/j.issn.1009-3419.2023.101.30
- Author:
Jiangong XU
1
Author Information
1. Department of Thoracic Surgery, The Third Affiliated Hospital of Xinxiang Medical College, Xinxiang 453003, China.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Lung neoplasms;
Metastasis;
TPX2;
miR-218-5p;
p53
- MeSH:
Humans;
Lung Neoplasms/genetics*;
Tumor Suppressor Protein p53/genetics*;
Adenocarcinoma of Lung/genetics*;
Adenocarcinoma/genetics*;
Cell Proliferation/genetics*;
MicroRNAs/genetics*;
Cell Movement/genetics*;
Gene Expression Regulation, Neoplastic;
Cell Line, Tumor;
Microtubule-Associated Proteins/genetics*;
Cell Cycle Proteins/genetics*
- From:
Chinese Journal of Lung Cancer
2023;26(10):721-731
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND:Lung adenocarcinoma (LUAD) is a major subtype of lung cancer, and its treatment and diagnosis remain a hot research topic. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is highly expressed in a variety of cancer cells and may be associated with the progression of LUAD. This study aimed to investigate the effect of TPX2 on the malignant progression of LUAD cells and the regulatory mechanisms.
METHODS:The expression of gene TPX2 in LUAD tissues from The Cancer Genome Atlas (TCGA) database was analyzed by bioinformatics analysis techniques. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of TPX2 and miR-218-5p in human lung normal cell lines and human LUAD cell lines. Western blot was used to detect TPX2 protein expression in cell lines and its effect on the expression of key proteins in the p53 signaling pathway. The relationship between TPX2 and miR-218-5p was predicted using bioinformatics and verified by dual luciferase reporter gene assay. Cell counting kit-8 (CCK-8) assay, cell clone formation, cell scratching, Transwell assay, and flow cytometry were used to detect the effects of miR-218-5p and TPX2 on LUAD cell function.
RESULTS:TPX2 was significantly overexpressed in LUAD cells, and knockdown of TPX2 inhibited LUAD cell proliferation, migration, and invasion, promoted apoptosis and induced G2/M phase block, and promoted the expression of key proteins in the p53 signaling pathway. miR-218-5p, an upstream regulator of TPX2, could inhibit its expression. Overexpression of miR-218-5p eliminated the malignant development caused by high expression of TPX2, inhibited the malignant processes of LUAD cells such as proliferation and migration as well as promoted the p53 signaling pathway.
CONCLUSIONS:miR-218-5p targets and inhibits TPX2 expression and exerts an inhibitory effect on the malignant progression of LUAD cells via p53.
