Carbonic anhydrase IV inhibits cell proliferation in gastric cancer by regulating the cell cycle

Wang,Bujiang; Jiang,Haizhong; Wan,Xiangxiang; Wang,Yaqing; Zheng,Xiaocao; Li,Peifei; Guo,Junming; Ding,Xiaoyun; Song,Haojun

doi:10.3892/ol.2020.11865

Carbonic anhydrase IV inhibits cell proliferation in gastric cancer by regulating the cell cycle

Authors:
- Bujiang Wang
- Haizhong Jiang
- Xiangxiang Wan
- Yaqing Wang
- Xiaocao Zheng
- Peifei Li
- Junming Guo
- Xiaoyun Ding
- Haojun Song
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Affiliations: Department of Gastroenterology, Laboratory of Digestive Diseases, Ningbo First Hospital, Ningbo, Zhejiang 315010, P.R. China, Department of Gastroenterology, The Third Hospital of Nanchang, Nanchang, Jiangxi 330002, P.R. China, Laboratory of Molecular Medicine, Ningbo First Hospital, Ningbo, Zhejiang 315010, P.R. China, Department of Histopathology, Ningbo Diagnostic Pathology Center, Ningbo, Zhejiang 315010, P.R. China, Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, P.R. China
Published online on: July 15, 2020 https://doi.org/10.3892/ol.2020.11865
Article Number: 4
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Carbonic anhydrase IV (CA4) is silenced in colorectal cancer. However, the effect of CA4 on the development of gastric cancer (GC) is poorly understood. The present study aimed to determine the role of CA4 in GC tumorigenesis and its underlying molecular mechanism. The levels of CA4 in GC cells and tissues were evaluated by reverse transcription‑quantitative PCR and immunohistochemistry. CA4 expression was suppressed in GC cells and tissues compared with adjacent healthy tissues and normal human gastric epithelial cells, respectively. This reduced expression was significantly associated with tumor size, invasion and differentiation. Analyses with a real‑time cell analyzer and clonogenic assays were conducted to validate the impact of CA4 on GC cell lines (AGS and HGC‑27) and normal human gastric epithelial cell line (GES‑1) proliferation. The effects of CA4 on the cell cycle in GC cells were determined by flow cytometry. The levels of CA4 and cell cycle‑associated proteins were confirmed by western blotting. CA4 overexpression inhibited GC cell proliferation and reduced colony‑forming ability, arrested the cell cycle in the G2/M phase, inhibited cyclin B1 and cyclin‑dependent kinase 2 expression and induced p21 expression. These results indicate that CA4 may serve an important role in GC tumorigenesis by inhibiting cellular proliferation via regulating the expression of cell cycle‑associated proteins. CA4 may serve as a diagnostic biomarker and a potential therapeutic target in GC.

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