Hoxa10-flox Mouse

Hoxa10, belonging to the HOX gene family, is essential for embryonic development, playing a role in patterning the uterus during embryogenesis [2,6]. In the adult endometrium, its expression is menstrual cycle-dependent, regulated by ovarian steroid hormones and embryonic signals, and is crucial for uterine receptivity, embryo implantation, and stromal cell decidualization [2,6]. It is also involved in various signaling pathways and cell cycle regulation [2]. Genetic models like Gdf5-HiBiT knock-in mice have been used to study its functions [4].

In gastric cancer, Hoxa10 is upregulated, especially in patients with lymph node metastasis. It promotes cell migration, invasion, and lung metastasis through epithelial-mesenchymal transition (EMT), mediated by the TGFB2/Smad/METTL3 signaling axis [1]. In endometrial disorders such as endometriosis, hypermethylation of Hoxa10 is observed, leading to its downregulation, which may contribute to endometrial epithelial cell proliferation and failure of stromal cell decidualization [2,3,5]. In prostate cancer, Hoxa10 expression is inversely associated with tumor differentiation, and high expression is related to improved biochemical recurrence-free survival, suggesting a tumor-suppressive role [7]. In endometrial stromal cells, Hoxa10 regulates cholesterol synthesis-related genes [8]. In endometrial cells of women with recurrent implantation failure and unexplained recurrent miscarriage, Hoxa10 improves endometrial receptivity by upregulating E-cadherin [9].

In conclusion, Hoxa10 is vital for normal development, especially in uterine-related functions. Its dysregulation is associated with multiple diseases, including gastric cancer, endometrial disorders, and prostate cancer. Studies using mouse models and cell lines have provided insights into its functions in these disease conditions, highlighting its potential as a therapeutic target or biomarker.