Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan 250021, Shandong, China.
Department of Critical Medicine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 264003, Shandong, China.
Biosci Rep. 2020 Apr 30;40(4). 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.
肺癌是发病率和死亡率最高的恶性肿瘤类型，非小细胞肺癌（NSCLC）是最常见的病理类型。GINS 复合物亚基 2（GINS2）是 GINS 家族的一员，与 DNA 复制和损伤密切相关，参与细胞周期调控，在细胞增殖和凋亡中发挥关键作用。本研究旨在探讨 GINS2 在 NSCLC 发生发展中的作用及其潜在的分子机制。结果表明，GINS2 在 NSCLC 组织和细胞系中显著增加。敲低 GINS2 可显著降低细胞增殖，导致 G2/M 期细胞周期阻滞。敲低 GINS2 逆转了诺考达唑对细胞周期蛋白依赖性激酶 1（CDK1）和细胞周期蛋白 B1 水平的影响。同时，敲低 GINS2 可显著提高细胞凋亡率和凋亡相关蛋白 Bax 的表达，并降低 Bcl-2 的表达。此外，GINS2 敲低诱导 p53 和生长停滞和 DNA 损伤 45A（GADD45A）水平升高。GINS2-siRNA 与 p53-siRNA 共转染或 GINS2-siRNA 与 GADD45A-siRNA 共转染部分逆转了 GINS2 敲低对细胞增殖和凋亡的影响。综上所述，这些结果表明，敲低 GINS2 通过下调细胞增殖，诱导 G2/M 期细胞周期阻滞和增加细胞凋亡，可能通过 p53/GADD45A 通路。
