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.

Combined targeting of KRT23 and NCCRP1 as a potential novel therapeutic approach for the treatment of triple-negative breast cancer

“…Breast cancers characterized by triple-negative status tend to be more malignant and have a poorer prognosis (1,2,(4)(5)(6)19,20). To decrease the mortality rate and improve the prognosis of breast cancer patients, a model for predicting breast cancer risk should be developed.…”

“…In the absence of ER, PR, and Her2/ neu, optimizing the therapeutic management of patients is difficult (2,3). Despite the improvements in combined surgical and radiochemotherapy (4)(5)(6), there remains a pressing need for new therapeutic approaches and molecular targets.…”

Targeting the nucleic acid oxidative damage repair enzyme MTH1: a promising therapeutic option

“…In human breast cancer cells, particularly MCF7-R, the knockdown of MTH1 activated the expression of the cell cycle protein-dependent kinase inhibitory protein p21. This led to increased sensitivity of MCF7-R cells to gemcitabine, suggesting that silencing the MTH1 gene can enhance the sensitivity of breast cancer cells, potentially serving as a novel adjuvant therapy for targeting drug-resistant tumors ( Wen et al, 2021 ). Similarly, in the study of triple negative breast cancer (TNBC) development, the actin fiber-associated protein 1-antisense RNA1 (AFAP1-AS1) was identified as targeting miR-145 to regulate MTH1 expression, thereby promoting proliferation and invasion.…”

Potential role of exitron‐containing homeobox genes in cancer

“…Among the HOX genes discussed so far, HOXD8 has the most contradictory roles. Through different mechanisms, HOXD8 was a tumor suppressor in breast (Wen et al, 2021; Zhang et al, 2021), neuroblastoma (Y. Zha et al, 2012), and colorectal cancer (Mansour & Senga, 2017). However, HOXD8 was found to be recurrently overexpressed in lung squamous carcinoma (Bao et al, 2016) and cisplatin chemoresistant ovarian cancer (Sun et al, 2018).…”