Zmym1-KO Mouse

ZMYM1, zinc finger MYM-type containing 1, is involved in multiple biological processes. It is regulated by METTL3-mediated N6-methyladenosine (m6A) modification, which impacts its mRNA stability. This m6A-related regulation is associated with the epithelial-mesenchymal transition (EMT) and metastasis pathways, and thus is of great importance in cancer biology [1,3].

In gastric cancer, METTL3-mediated m6A modification of ZMYM1 mRNA enhances its stability through the HuR-dependent pathway. ZMYM1 then binds to and represses the E-cadherin promoter by recruiting the CtBP/LSD1/CoREST complex, facilitating EMT and metastasis [1]. In liver hepatocellular carcinoma, the METTL3-m6A-ZMYM1 axis may accelerate metastasis by inactivating the RAS/ERK/c-FOS pathway, reducing E-cadherin expression, and increasing N-cadherin and Vimentin expressions [3]. In neuroblastoma, genetic variants may dysregulate ZMYM1 expression, potentially leading to malignant transformation by affecting neuronal differentiation [2].

In summary, ZMYM1, regulated by m6A modification, plays a crucial role in cancer-related biological processes such as EMT, metastasis, and neuronal differentiation in cancer development. Understanding the functions of ZMYM1 through these model-based studies provides insights into potential therapeutic targets for anti-metastatic strategies in gastric and liver cancers, as well as into the pathogenesis of neuroblastoma [1,2,3].

References:

1. Yue, Ben, Song, Chenlong, Yang, Linxi, Zhang, Zizhen, Zhao, Gang. 2019. METTL3-mediated N6-methyladenosine modification is critical for epithelial-mesenchymal transition and metastasis of gastric cancer. In Molecular cancer, 18, 142. doi:10.1186/s12943-019-1065-4. https://pubmed.ncbi.nlm.nih.gov/31607270/

2. Tirelli, Matilde, Bonfiglio, Ferdinando, Cantalupo, Sueva, Iolascon, Achille, Capasso, Mario. 2024. Integrative genomic analyses identify neuroblastoma risk genes involved in neuronal differentiation. In Human genetics, 143, 1293-1309. doi:10.1007/s00439-024-02700-2. https://pubmed.ncbi.nlm.nih.gov/39192051/

3. Chen, Wenbiao, Meng, Yiteng, Zhan, Shenggang, Wang, Lisheng, Yao, Jun. 2025. An exploration on the involvement of the methyltransferase like 3-m6A‑zinc finger MYM-type containing 1 axis in the progression of liver hepatocellular carcinoma. In International journal of biological macromolecules, 309, 142820. doi:10.1016/j.ijbiomac.2025.142820. https://pubmed.ncbi.nlm.nih.gov/40187452/