Runx3, a runt-related transcription factor, plays regulatory roles in cell proliferation, development, cell cycle progression, differentiation, apoptosis, immunity and epithelial-mesenchymal transition [1,2]. It can integrate signals from pathways like Wnt, TGFβ and Hippo-YAP to influence cell fate decisions [2].

Targeted inactivation of Runx3 in the mouse lung induces adenomas and shortens the latency of ADC formation induced by oncogenic K-Ras, suggesting its role in oncogenic surveillance at the restriction point of the cell cycle [3]. Runx3-knockout mice experiments show that Runx3 deficiency reduces CD8 + T infiltration and the differentiation of effector T and memory T cells, and also decreases CCR3 and CCR5 levels, indicating its importance in CD8 + T-cell function [4]. In myeloid transformation, although Runx3 deletion in mice did not lead to lethal hematological diseases despite myeloid cell expansion, overexpression of RUNX3 in premalignant stem cells with driver genetic mutations can lead to transformation by inhibiting RUNX1 and activating oncogenic pathways like MYC [5].

In conclusion, Runx3 is a crucial transcription factor involved in multiple biological processes. Gene-knockout mouse models have revealed its significance in cancer development, especially in lung adenocarcinomas, and in immune cell function, particularly CD8 + T-cell infiltration and differentiation. Understanding Runx3 through these models provides insights into the mechanisms of related diseases and may offer potential therapeutic targets.