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Small Proline-Rich Protein 2B Facilitates Gastric Adenocarcinoma Proliferation via MDM2-p53/p21 Signaling Pathway

Authors Yao L, Yan J, Cheng F, Gan L, Huang Y, Zheng L, Fang N

Received 10 September 2020

Accepted for publication 13 January 2021

Published 26 February 2021 Volume 2021:14 Pages 1453—1463

DOI https://doi.org/10.2147/OTT.S281032

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Takuya Aoki


Ling Yao,1 Jinhua Yan,2 Fei Cheng,1 Lihong Gan,1 Yaqin Huang,1 Li Zheng,1 Nian Fang1

1Department of Gastroenterology, Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi Province, People’s Republic of China; 2Department of Hematology, Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi Province, People’s Republic of China

Correspondence: Nian Fang
Department of Gastroenterology, Third Affiliated Hospital of Nanchang University, No. 128 Xiangshan North Road, Nanchang, 330008, Jiangxi Province, People’s Republic of China
Tel +86-0791-88862387
Email [email protected]

Background: The small proline-rich protein 2B (SPRR2B) was firstly reported as a member of the cross-linked envelope protein in keratinocytes. The effect of SPRR2B in gastric adenocarcinoma (GC) remains unclear. This study initially explored the clinical significance of SPRR2B in GC patients as well as its role in tumor progression.
Methods: Immunohistochemistry was performed to characterize the expression of SPRR2B in GC tissues and adjacent tissues. The relationship between SPRR2B expression and clinicopathological features of GC patients was analyzed by Chi-square test. Kaplan-Meier method and Cox regression analyses were utilized to identify the prognostic factors of GC. Overexpression and knockdown assays were conducted to investigate possible signaling pathways downstream of SPRR2B. Flow cytometry assays were performed to evaluate cell cycle and apoptosis. Xenograft experiments were performed to validate tumor-related role of SPRR2B in vivo.
Results: Both mRNA and protein levels of SPRR2B in cancerous tissue were significantly higher than those in non-cancerous tissues. Meanwhile, SPRR2B expression was significantly associated with tumor size and tumor stage. Survival analysis revealed SPRR2B as one of the independent prognosis factors for overall survival of GC patients. Cellular and xenografts data implicated that silencing SPRR2B blocked the cell cycle of GC cells perhaps through MDM2-p53/p21-CDK1 pathway, while overexpressing SPRR2B exhibited opposite effects.
Conclusion: Our data suggest that SPRR2B may serve as a novel prognostic marker in GC, which functions at least partially by MDM2-p53/p21-CDK1 signaling pathway.

Keywords: gastric adenocarcinoma, MDM2, prognosis, proliferation, SPRR2B

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