J Cancer 2021; 12(1):99-110. doi:10.7150/jca.46744

Research Paper

GINS2 attenuates the development of lung cancer by inhibiting the STAT signaling pathway

Dianmin Sun1,5, Yuanyuan Zong2,5, Jinling Cheng3, Zhenxiang Li4,5, Ligang Xing4,5✉, Jinming Yu4,5✉

1. Department of Thoracic Surgery, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China
2. Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250117, China
3. Department of Gastroenterology, Shandong Provincial Western Hospital, Jinan, Shandong 250117, China
4. Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong 272173, China
5. Shandong University, Jinan, Shandong 250117, China

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Citation:
Sun D, Zong Y, Cheng J, Li Z, Xing L, Yu J. GINS2 attenuates the development of lung cancer by inhibiting the STAT signaling pathway. J Cancer 2021; 12(1):99-110. doi:10.7150/jca.46744. Available from https://www.jcancer.org/v12p0099.htm

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Abstract

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.

Keywords: GINS2, STAT, lung cancer, proliferation, apoptosis