J Cancer 2020; 11(16):4662-4670. doi:10.7150/jca.38386 This issue Cite

Research Paper

GINS2 affects cell viability, cell apoptosis, and cell cycle progression of pancreatic cancer cells via MAPK/ERK pathway

Miao Zhang1#, Saifei He1#, Xing Ma2, Ying Ye1, Guoyu Wang2, Juhua Zhuang2, Yanan Song1✉, Wei Xia2✉

1. Central Laboratory, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China.
2. Department of Nuclear Medicine, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China.
#These authors have contributed equally to this work and should be considered as co-first authors.

Citation:
Zhang M, He S, Ma X, Ye Y, Wang G, Zhuang J, Song Y, Xia W. GINS2 affects cell viability, cell apoptosis, and cell cycle progression of pancreatic cancer cells via MAPK/ERK pathway. J Cancer 2020; 11(16):4662-4670. doi:10.7150/jca.38386. https://www.jcancer.org/v11p4662.htm
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Abstract

Background and Objective: GINS complex subunit 2 (GINS2), a member of the GINS complex, is involved in DNA replication. GINS2 is upregulated in a variety of aggressive tumors, such as leukemia, breast cancer, and cervical cancer. However, the role of GINS2 in pancreatic cancer has still remained elusive. In this study, PANC-1 and BxPC-3 cell lines were chosen to perform experiments in vitro. Additionally, the effects of GINS2 interference on the cell viability, cell apoptosis, cell cycle, and tumor growth in nude mice were analyzed.

Methods: We utilized pancreatic cancer cell lines that knocked down GINS2 expression using small interference RNA (siRNA) and evaluated GINS2 expression using Western blot analysis. To explore the function of GINS2 in pancreatic cancer cell lines in vitro, MTT assay and flow cytometry were used. Additionally, we investigated the potential mechanism of GINS2 interference by identifying the MAPK/ERK pathway using Western blotting. Finally, PANC-1 cells with GINS2 knockdown were subcutaneously injected into nude mice to evaluate the effects of GINS2 on tumor growth in vivo.

Results: It was unveiled that GINS2 interference inhibited cell viability, induced cell cycle arrest at G1 phase, and enhanced apoptosis of pancreatic cancer cell lines. Western blot assay indicated that GINS2 interference increased the expression level of Bax, while the expression level of Bcl-2 was remarkably decreased. In addition, the expression levels of CDK4, CDK6, and Cyclin D1 were significantly reduced after treatment with GINS2 siRNA. Furthermore, GINS2 interference drastically attenuated the expression levels of MEK, p-MEK, ERK, and p-ERK, belonging to the MAPK/ERK pathway. The results of an established cancer xenograft model revealed that nude mice transplanted with cells expressing negative control (NC) exhibited larger and heavier tumors, while volume and weight of tumor were remarkably reduced in ones transplanted with cells expressing GINS2 siRNA.

Conclusions: GINS2 interference inhibited cell viability, induced cell cycle arrest, and promoted cell apoptosis of pancreatic cancer cell lines via the MAPK/ERK pathway, and our findings may be valuable for treating pancreatic cancer.

Keywords: Pancreatic cancer, GINS2, MAPK/ERK pathway


Citation styles

APA
Zhang, M., He, S., Ma, X., Ye, Y., Wang, G., Zhuang, J., Song, Y., Xia, W. (2020). GINS2 affects cell viability, cell apoptosis, and cell cycle progression of pancreatic cancer cells via MAPK/ERK pathway. Journal of Cancer, 11(16), 4662-4670. https://doi.org/10.7150/jca.38386.

ACS
Zhang, M.; He, S.; Ma, X.; Ye, Y.; Wang, G.; Zhuang, J.; Song, Y.; Xia, W. GINS2 affects cell viability, cell apoptosis, and cell cycle progression of pancreatic cancer cells via MAPK/ERK pathway. J. Cancer 2020, 11 (16), 4662-4670. DOI: 10.7150/jca.38386.

NLM
Zhang M, He S, Ma X, Ye Y, Wang G, Zhuang J, Song Y, Xia W. GINS2 affects cell viability, cell apoptosis, and cell cycle progression of pancreatic cancer cells via MAPK/ERK pathway. J Cancer 2020; 11(16):4662-4670. doi:10.7150/jca.38386. https://www.jcancer.org/v11p4662.htm

CSE
Zhang M, He S, Ma X, Ye Y, Wang G, Zhuang J, Song Y, Xia W. 2020. GINS2 affects cell viability, cell apoptosis, and cell cycle progression of pancreatic cancer cells via MAPK/ERK pathway. J Cancer. 11(16):4662-4670.

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