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

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.

Transcriptomic landscape of endothelial cells: Key tumor microenvironment components indicating variable clinical outcomes in pancreatic ductal adenocarcinoma

“…15 The role of CA4 in gastric cancer (GC) tumorigenesis was investigated in this study by evaluating the levels of CA4 in GC cells and tissues and conducting analyses to determine its impact on GC cell lines. 16 The results demonstrate that CA4 may serve as a diagnostic biomarker and potential therapeutic target in GC by inhibiting cellular proliferation via regulating the expression of cell cycle-associated proteins. The MT1F gene is a member of the metallothionein (MT) gene family.…”

“…While the previous research has examined the role of CA4 in physiological processes such as acid–base balance and respiration, 14 recent studies have also suggested that CA4 may play a role in cancer development and progression 15 . The role of CA4 in gastric cancer (GC) tumorigenesis was investigated in this study by evaluating the levels of CA4 in GC cells and tissues and conducting analyses to determine its impact on GC cell lines 16 . The results demonstrate that CA4 may serve as a diagnostic biomarker and potential therapeutic target in GC by inhibiting cellular proliferation via regulating the expression of cell cycle‐associated proteins.…”

A New Risk Model Based on 7 Quercetin-Related Target Genes for Predicting the Prognosis of Patients With Lung Adenocarcinoma

“…Studies have found that NEK2, TOP2A, PLK1, CA4, CDK5R1, AURKB, and F2 have important regulatory roles in cell cycle, DNA replication, homologous recombination, and others (Chabalier-Taste et al, 2016;Fan et al, 2019;Zeng et al, 2019;Wang et al, 2020;Ha et al, 2022). The expression level of NEK2 in human gastric cancer (GC) tissues is significantly upregulated.…”

PADI4 promotes epithelial-mesenchymal transition(EMT) in gastric cancer via the upregulation of interleukin 8

“…The distance between the tumour tissues and normal adjacent mucosal tissues was 5 cm. The inclusion and exclusion criteria for the patients were based on the method of Wang B et al [ 20 ].…”