Homeobox protein C4 regulates the proliferation, migration and invasion of gastric cancer cells by integrin β1
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Abstract:
[Abstract] Objective: To investigate the expression of homeobox protein C4 (HOXC4) in gastric cancer tissues and cells, as well as its effects on the proliferation, migration and invasion of gastric cancer cells and the underlying mechanisms. Methods: The cancer and adjacent tissue specimens surgically removed from 16 patients with advanced gastric cancer at the Department of Oncology, Nanyang First People’s Hospital, between May 2020 and April 2021 were collected. Additionally, human normal gastric epithelial cells (GES-1) and gastric cancer cell lines (AGS, SGC-790, and MGC-803) were included. Western blot (WB) was performed to detect HOXC4 expression in gastric cancer tissues and cells. RNA interference technology was used to knockdown or overexpress HOXC4 in SGC-790 and AGS cells, with experimental groups divided as follows: the sh-HOXC4#1 group, sh-HOXC4#2 group, sh-Con group, sh-HOXC4 + pc-integrin β1 group, pc-HOXC4 group, pc-Con group, and pc-HOXC4 + pc-integrin β1 group. EdU assay, CCK-8 assay, and Transwell assay were employed to evaluate the effects of HOXC4 knockdown or overexpression on cell viability, proliferation, migration,invasion, and integrin β1 expression in each group. A tumor-bearing mouse model was established using HOXC4-knockdown AGS cells to observe the impact of HOXC4 knockdown on tumor volume and the expressions of Ki67 and integrin β1 proteins in xenograft tissues. Results: The expression of HOXC4 in gastric cancer tissues and cells was significantly up-regulated (all P < 0.01). Compared with those in the sh-Con group, the expression levels of HOXC4 and integrin β1 in SGC-790 and AGS cells, and the cell viability, proliferation, migration and invasion ability decreased significantly in sh-HOXC4#1 and sh-HOXC4#2 groups (all P < 0.01).Compared with those in the sh-HOXC4 group, the cell viability, invasion and migration abilities of cells in the sh-HOXC4 + pc-integrin β1 group increased significantly (all P < 0.01). Compared with those in the pc-Con group, the cell viability, invasion and migration abilities of cells in the pc-HOXC4 group increased significantly (all P < 0.01). Compared with those in the pc-HOXC4 group, the cell viability, invasion and migration abilities of cells in the pc-HOXC4+integrin β1-shRNA group decreased significantly (all P < 0.01). Compared with those in the sh-Con group, the tumor grew slowly, and the volume decreased, and the expressions of Ki67 and integrin β1 decreased significantly in the sh-HOXC4#1 and sh-HOXC4#2 groups (all P < 0.01). Conclusion: The expression of HOXC4 is up-regulated in gastric cancer tissues and cells, and it promotes the proliferation, migration and invasion of gastric cancer cells by activating the integrin β1 signaling pathway.