Zmynd8, also known as Zinc finger MYND-type containing 8, is a transcription factor, histone H3-interacting protein, and a putative chromatin reader/effector. It plays a crucial role in regulating transcription during normal cellular growth and is involved in various biological processes and pathways. Mutations and altered expression of Zmynd8 are associated with the development and progression of cancer [2].

In breast cancer, Zmynd8 was found to be upregulated in breast cancer stem cells (BCSCs). Gene-related functional studies in mouse models showed that Zmynd8 reduces ROS and iron to inhibit ferroptosis in aldehyde dehydrogenase-high (ALDHhi) BCSCs, leading to BCSC expansion and tumor initiation. This occurs through a two-fold post-translational regulation of nuclear factor erythroid 2-related factor 2 (NRF2), increasing NRF2 protein stability and enhancing antioxidant gene transcription [1]. In acute myeloid leukemia (AML), Zmynd8 directly activates IRF8 in parallel with the MYC proto-oncogene through their lineage-specific enhancers, and is essential for AML proliferation in vitro and in vivo [3].

In conclusion, Zmynd8 has diverse essential biological functions. Its role in promoting cancer development, such as in breast cancer and AML, has been revealed through model-based research, especially KO/CKO mouse models. Understanding Zmynd8's functions contributes to a deeper understanding of cancer-related biological processes and may provide new therapeutic targets for these diseases.