Wen Xiaoyun, Chen Yu, Fang Xiansong
Department of Clinical Laboratory, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.
Department of Blood Transfusion, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.
Exp Ther Med. 2021 Sep;22(3):1006. doi: 10.3892/etm.2021.10439. Epub 2021 Jul 15.
Breast cancer is one of the most common malignant tumors in women. Although a number of homeobox (HOX) genes are known to serve an important role in breast cancer, the role of HOXD8 in breast cancer remains unclear. The aim of the present study was to investigate the role of HOXD8 in the physiological behaviors of breast cancer cells. The Gene Expression Profiling Interactive Analysis database was used to analyze the expression of HOXD8 in patients with breast cancer and in healthy subjects. Western blotting was performed to determine the expression levels of HOXD8 in several breast cancer cell lines; subsequently, HOXD8 expression was knocked down and overexpressed in MCF-7 cells. Cell Counting Kit-8, colony formation, wound healing and Transwell assays were used to evaluate the effects of HOXD8 on breast cancer cell viability, proliferation, migration and invasion, respectively. Chromatin immunoprecipitation and dual-luciferase reporter assays were conducted to identify the binding sites between HOXD8 and inhibitor of apoptosis-like protein-2 (ILP2). In addition, ILP2 expression levels were knocked down in MCF-7 cells. The results demonstrated that the expression levels of HOXD8 were significantly downregulated in breast cancer tissues and cell lines, and that the overexpression of HOXD8 inhibited the proliferation, invasion and migration of cancer cells. HOXD8 was shown to bind to the ILP2 promoter to regulate the expression of ILP2. Furthermore, ILP2 knockdown reversed the effects of HOXD8 knockdown on breast cancer cell proliferation, invasion and migration. In conclusion, the findings of the present study suggested that HOXD8 may inhibit the proliferation, migration and invasion of breast cancer cells by downregulating ILP2 expression.
乳腺癌是女性最常见的恶性肿瘤之一。尽管已知一些同源框（HOX）基因在乳腺癌中发挥重要作用，但HOXD8在乳腺癌中的作用仍不清楚。本研究的目的是探讨HOXD8在乳腺癌细胞生理行为中的作用。利用基因表达谱交互式分析数据库分析HOXD8在乳腺癌患者和健康受试者中的表达情况。采用蛋白质免疫印迹法检测几种乳腺癌细胞系中HOXD8的表达水平；随后，在MCF-7细胞中敲低和过表达HOXD8。分别采用细胞计数试剂盒-8、集落形成、伤口愈合和Transwell实验评估HOXD8对乳腺癌细胞活力、增殖、迁移和侵袭的影响。进行染色质免疫沉淀和双荧光素酶报告基因实验，以确定HOXD8与凋亡样蛋白-2（ILP2）抑制剂之间的结合位点。此外，在MCF-7细胞中敲低ILP2表达水平。结果表明，HOXD8在乳腺癌组织和细胞系中的表达水平显著下调，HOXD8的过表达抑制了癌细胞的增殖、侵袭和迁移。HOXD8被证明与ILP2启动子结合以调节ILP2的表达。此外，ILP2敲低逆转了HOXD8敲低对乳腺癌细胞增殖、侵袭和迁移的影响。总之，本研究结果表明，HOXD8可能通过下调ILP2表达来抑制乳腺癌细胞的增殖、迁移和侵袭。
