[摘 要] 目的：探讨同源框蛋白C4（HOXC4）在胃癌组织和细胞中的表达及其对胃癌细胞增殖、迁移与侵袭的作用及其机制。 方法：收集2020年5月至2021年4月期间在南阳市第一人民医院肿瘤科手术切除的16例进展期胃癌患者的癌及癌旁组织标本， 以及人胃正常上皮细胞GES-1和胃癌细胞AGS、SGC-790和MGC-803，采用WB法检测胃癌组织和细胞中HOXC4的表达。通过 RNA干扰技术对SGC-790及AGS细胞中HOXC4进行敲低或过表达，实验分为sh-HOXC4#1组、sh-HOXC4#2组、sh-Con组、 sh-HOXC4 + pc-integrin β1组、pc-HOXC4组、pc-Con组、pc-HOXC4 + pc-integrin β1组。利用EdU、CCK-8、Transwell实验分别检 测敲低或过表达HOXC4对各组细胞活力、增殖、侵袭、迁移和integrin β1表达的影响。用敲低HOXC4的胃癌AGS细胞构建荷瘤 小鼠模型，观察敲低HOXC4对移植瘤体积及组织中Ki67和integrin β1蛋白表达的影响。结果：胃癌组织和细胞中HOXC4的表 达均显著上调（均P < 0.01）。与sh-Con组相比，sh-HOXC4#1组和sh-HOXC4#2组SGC-790及AGS细胞中HOXC4、integrin β1蛋 白表达水平，以及细胞的活力、增殖、迁移及侵袭能力均显著降低（均P < 0.01）。与sh-HOXC4组相比，sh-HOXC4 + pc-integrin β1 组细胞活力、增殖、迁移及侵袭能力均显著增加（均P < 0.01）；与pc-Con组相比，pc-HOXC4组细胞活力、侵袭及迁移能力均显著 增加（均P < 0.01）；与pc-HOXC4组相比，pc-HOXC4 + pc-integrin β1组细胞活力、迁移及侵袭能力均显著降低（均P < 0.01）。与 sh-Con组相比，sh-HOXC4#1组和sh-HOXC4#2组小鼠移植瘤生长缓慢、体积变小，组织中Ki67和integrin β1表达均显著降低（均 P < 0.01）。结论：HOXC4在胃癌组织与细胞中表达上调，其通过激活integrin β1信号促进胃癌细胞的增殖、迁移与侵袭。

[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.

河南省医学科技攻关项目（No. SB201901101）