Knockdown of GINS2 inhibits proliferation and promotes apoptosis through the p53/GADD45A pathway in non-small-cell lung cancer

• Published in: Bioscience reports 2020-04, Vol.40 (4)
• Main Authors: Chi, Feng, Wang, Zhou, Li, Yuzhu, Chang, Ning
• Format: Article
• Language: English
• Subjects: Apoptosis - genetics; Cancer; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - surgery; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell Proliferation - genetics; Chromosomal Proteins, Non-Histone - genetics; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Lung - pathology; Lung - surgery; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lung Neoplasms - surgery; M Phase Cell Cycle Checkpoints; Pneumonectomy; RNA, Small Interfering - metabolism; Signal Transduction - genetics; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/bsr20193949

Lung cancer is a malignant tumour type with the highest morbidity and mortality, and non-small-cell lung cancer (NSCLC) is the most common pathological type. GINS complex subunit 2 (GINS2) is a member of the GINS family and is closely related to DNA replication and damage, participates in cell cycle regulation and plays a key role in cell proliferation and apoptosis. In the present study, we aimed to explore the role and underlying molecular mechanism of GINS2 in the development of NSCLC. The results showed that GINS2 is significantly increased in NSCLC tissues and cell lines. Knockdown of GINS2 significantly decreases cell proliferation, causing G2/M phase cell cycle arrest. Knockdown of GINS2 reverses the effect of nocodazole on the levels of cyclin-dependent kinase 1 (CDK1) and cyclin-B1. Meanwhile, knockdown of GINS2 significantly elevates the apoptosis rate and apoptosis-related protein Bax and decreases Bcl-2. In addition, GINS2 knockdown induces an increase in the levels of p53 and growth arrest and DNA damage 45A (GADD45A). Co-transfection with GINS2-siRNA and siRNA against p53 (p53-siRNA) or co-transfection with GINS2-siRNA and siRNA against GADD45A (GADD45A-siRNA) partially reverses the effects of GINS2 knockdown on cell proliferation and apoptosis. Taken together, these results indicate that GINS2 knockdown down-regulates cell proliferation, induces G2/M phase cell cycle arrest and increases apoptosis, possibly through the p53/GADD45A pathway.