Sun Dianmin, Zong Yuanyuan, Cheng Jinling, Li Zhenxiang, Xing Ligang, Yu Jinming
Department of Thoracic Surgery, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.
Shandong University, Jinan, Shandong 250117, China.
J Cancer. 2021 Jan 1;12(1):99-110. doi: 10.7150/jca.46744. eCollection 2021.
GINS complex subunit 2 (GINS2) controls DNA replication. GINS2 expression is upregulated in several kinds of aggressive tumors. However, the effect of GINS2 in lung cancer remains unclear. We performed TCGA database analysis to confirm the clinical significance of GINS2 in lung cancer. After silencing GINS2 in A549 cells, we performed MTT assays, flow cytometry assays, colony formation assays, cell cycle analyses and RNA sequence analysis to elucidate the effect of GINS2 on lung cancer. Moreover, we assessed tumor growth and analyzed body fluorescence in mice as a measure of tumor burden. The TCGA database analysis demonstrated that GINS2 mRNA and protein was highly expressed in three kinds of lung cancer tissues. Subsequently, knockdown of GINS2 inhibited cell proliferation, colony formation, cell cycle arrest and apoptosis in A549 cells. On the other hand, we also investigated the effect of GINS2 on tumor formation in vivo. The analysis of nude mouse tumors showed that the tumor volume and weight of shGINS2 mice were significantly smaller than those of the control mice. To reveal the mechanism of GINS2 in lung cancer, we collected A549 cells with GINS2 knockdown to examine the downstream gene expression changes. The results showed that STAT1 and STAT2 mRNA and protein expression were significantly upregulated after GINS2 knockdown in A549 cells. Our results suggest that GINS2 inhibits the proliferation of lung cancer cells by inhibiting the STAT signaling pathway, which may be a potential biomarker for the diagnosis or prognosis of lung cancer.
GINS复合体亚基2（GINS2）控制DNA复制。GINS2在几种侵袭性肿瘤中表达上调。然而，GINS2在肺癌中的作用仍不清楚。我们进行了TCGA数据库分析，以证实GINS2在肺癌中的临床意义。在A549细胞中沉默GINS2后，我们进行了MTT试验、流式细胞术试验、集落形成试验、细胞周期分析和RNA序列分析，以阐明GINS2对肺癌的影响。此外，我们评估了肿瘤生长情况，并分析了小鼠体内的体荧光作为肿瘤负荷的指标。TCGA数据库分析表明，GINS2 mRNA和蛋白在三种肺癌组织中高表达。随后，GINS2的敲低抑制了A549细胞的增殖、集落形成、细胞周期停滞和凋亡。另一方面，我们还研究了GINS2对体内肿瘤形成的影响。裸鼠肿瘤分析表明，shGINS2小鼠的肿瘤体积和重量明显小于对照小鼠。为了揭示GINS2在肺癌中的作用机制，我们收集了GINS2敲低的A549细胞，以检测下游基因表达的变化。结果显示，A549细胞中GINS2敲低后，STAT1和STAT2 mRNA及蛋白表达显著上调。我们的结果表明，GINS2通过抑制STAT信号通路抑制肺癌细胞的增殖，这可能是肺癌诊断或预后的潜在生物标志物。
