Abstract
Previous studies have shown that regeneration gene 3 (reg3) is significantly expressed in gastric mucosa tissues with Helicobacter pylori (HP) cytotoxin-associated gene A (CagA)-positive (HP-CagA+). CagA-positive HP increases the risk of gastric cancer. The purpose of this study was to investigate the correlation between reg3 and HP-CagA+ and explore the effects of reg3 on the proliferation of gastric cancer cells and the development of tissues and organs. We analyzed the expression of reg3 in human tissues and organs. The results showed that reg3 expression in gastric tissues was significantly higher than that in other tissues and organs. In addition, reg3 influenced the prognosis of gastric, lung, and ovarian cancers. Immunohistochemical analysis indicated that the expression of reg3 and CagA in cancerous tissues was higher than that in adjacent tissues. HP-CagA+ infection of gastric cancer cells promotes reg3 expression, suggesting that reg3 may be a target gene of CagA in gastric cancer, which together affects the formation and development of gastric cancer. reg3 and CagA promote cell proliferation, and then affect the development of mouse tissues and organs by regulating G1/S phase transition of the cell cycle via the formation of the cell cycle-dependent complex CDK4/CyclinD1. This is the first study that shows the influence of CagA on the cell cycle and induction of cell proliferation by promoting reg3 expression.
Highlights
Gastric cancer is one of the most common malignant tumors in the world
These were estimated to have about 120 amino acids constituting a calcium-dependent carbohydrate recognition domain (CRD) [5], which are present in serum [6], extracellular matrix [7], and cell membrane [8], and C-type lectin on the cell membrane can participate in swallowing, cell adhesion, or humoral immune response [9,10]
The results indicated that the level of reg3 expression in gastric tissues, including the stomach, duodenum, and small intestine, was relatively higher than other the tissues and organs. reg3 is closely related to the occurrence of gastric cancer, and is an important growth gene and regulatory target in gastric cancer pathogenesis
Summary
Gastric cancer is one of the most common malignant tumors in the world. The five-year survival rate is less than 40%, thereby making it a serious threat to human health [1]. In human gastric mucosa tissues, the expression of Reg was significantly increased in the presence of CagA compared to CagA-negative H. pylori-infected individuals [15]. Studies involving transgenic mice have further supported the hypothesis that CagA may be a potential carcinogenic factor [20]. How reg interacts with CagA in the stomach and affects the occurrence and development of gastric cancer, as well as how to regulate downstream genes to induce tumors, have not been studied to date. The purpose of this study was to explore the carcinogenic mechanism of Reg and CagA and to provide some basis for cancer treatment
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