Nkx6-3, a transcription factor, is crucial for gastric mucosal epithelial differentiation. It is involved in pathways such as amyloid β (Aβ) production regulation, Wnt/β-catenin and Rho-GTPase signaling, and also impacts reactive oxygen species (ROS) production [1,3,6]. Genetic models, like gene knockout in mice, can be valuable for studying its functions.

In gastric-related studies, NKX6.3 depletion in human gastric epithelial cells led to multiple outcomes. It induced cell death, increased Aβ peptide oligomers production, and upregulated related proteins, causing gastric mucosal atrophy [1]. NKX6.3 depletion also promoted cell cycle progression, mitotic defects, genomic instability, and abnormal DNA replication and repair, contributing to gastric carcinogenesis [2,4]. Additionally, it led to abnormal expression of CDX2 and SOX2, potentially causing gastric-to-intestinal transdifferentiation, and activated AICDA/APOBEC family, resulting in genetic mutations in gastric epithelial cells [5,7].

In conclusion, Nkx6-3 is essential for maintaining gastric epithelial homeostasis, regulating mitotic integrity, genomic stability, and differentiation in the stomach. Studies using Nkx6-3 depletion models have significantly contributed to understanding its role in gastric mucosal atrophy and carcinogenesis, providing potential therapeutic targets for these gastric diseases [1-3,5-7,9].