Overexpression of HOXD8 inhibits the proliferation, migration and invasion of breast cancer cells by downregulating ILP2 expression.

Abstract

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.