Kdm3a, also known as lysine-specific histone demethylase 3A, is an H3K9me2/me1 histone demethylase in the KDM3 subfamily. It contains a catalytic Jumonji C domain at its C-terminus, a zinc-finger domain for DNA binding, and an LXXLL motif for interacting with nuclear receptors. Kdm3a promotes gene expression and is involved in multiple biological pathways, playing a significant role in various biological processes and diseases [1].

In cancer research, Kdm3A over-expression suppresses the tumor-intrinsic IFN response in gastric cancer. Inhibiting Kdm3A, either genomically or pharmacologically, activates endogenous retroviruses to promote IFN responses, reconfigures the dsRNA-MAVS-IFN axis, enhances CD8 T cell infiltration and function, and reduces regulatory T cells, reshaping the tumor microenvironment [2]. In colorectal cancer, its expression level in leukocyte samples may serve as a supplementary biomarker for diagnosis [3]. In osteosarcoma, Kdm3A promotes aerobic glycolysis and tumor development by regulating the transcription of SP1 and PFKFB4 [5]. In addition, in postnatal hippocampal neurogenesis, Kdm3a knockout in neural stem/progenitor cells hinders postnatal neurogenesis, compromising learning and memory abilities in mice. Kdm3a regulates the Wnt/β-catenin signaling pathway through dual mechanisms in neural stem/progenitor cells [4].

In conclusion, Kdm3a is a crucial regulator involved in multiple biological functions. Model-based research, especially gene knockout in mouse models, has revealed its significant roles in cancer, such as gastric, colorectal, and osteosarcoma, as well as in postnatal hippocampal neurogenesis. Understanding Kdm3a's functions provides insights into disease mechanisms and potential therapeutic targets.