Sema3A Alleviates the Malignant Behaviors of Gastric Cancer Cells by Inhibiting NRP-1

• Published in: Current molecular medicine Vol. 24; no. 7; p. 931
• Main Authors: Yang, Hongqiong, Zhou, Yaojun, Wang, Liangzhi, Lv, Mengjia, Sun, Jinling, Luo, Zhenguo, He, Junbo
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2024
• Subjects: Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation; Epithelial-Mesenchymal Transition - genetics; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Invasiveness; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Neuropilin-1 - genetics; Neuropilin-1 - metabolism; Semaphorin-3A - genetics; Semaphorin-3A - metabolism; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Sema3a; NRP-1; CCK-8; Gastric cancer; angiogenesis
• DOI: 10.2174/1566524023666230801124826

Semaphorin3A (Sema3a) is lowly expressed in the peripheral blood of gastric cancer patients, suggesting Sema3a may be involved in the progression of gastric cancer. Nevertheless, the specific role and the potential regulatory mechanism of Sema3a in gastric cancer is still obscure. Neuropilin-1 (NRP-1) has been reported to interact with Sema3a; herein, we intended to reveal the role and regulatory mechanism of Sema3a/neuropilin-1 (NRP-1) in gastric cancer progression. Cell transfection was carried out to regulate gene expression. CCK-8 and colony formation assays were applied to estimate cell proliferation. Scratch assay and transwell assay were conducted to assess the cell migration and invasion abilities. Angiogenesis ability was assessed using a tubule-forming assay. The expression of corresponding genes and proteins were detected by RT-qPCR and western blot, respectively. Data showed that Sema3a was downregulated in gastric cancer cells and NRP-1 was upregulated. Sema3a overexpression repressed NRP-1 level in AGS cells. Overexpression of Sema3a inhibited cell proliferation, migration, and invasion abilities as well as epithelial-mesenchymal transition (EMT) of AGS cells. Overexpression of Sema3a inhibited tube formation and reduced the expression of VEGFA/VEGFR2 in AGS cells. However, the effects of Sema3a overexpression on the malignant behaviors in AGS cells were partly reversed by NRP-1 overexpression. Additionally, Sema3a overexpression enhanced the inhibitory effects of Ramucirumab, an anti-VEGFR2 agent, on the proliferative, migratory, and invasive capabilities as well as EMT in AGS cells. In conclusion, Sema3a alleviates the proliferation, migration, invasion, and angiogenesis capabilities of gastric cancer cells via repressing NRP-1. This finding may provide potential targets for gastric cancer therapy.