Mef2d, or myocyte enhancer factor 2D, is a key transcription factor in the development of skeletal, cardiac, and neural tissues. It is involved in multiple biological processes such as embryonic development, nervous system regulation, muscle cell differentiation, and B-and T-cell development [4]. It can also participate in regulating immune responses through its effects on GATA3-dependent type-2 lymphocyte differentiation [2].

In acute lymphoblastic leukaemia (ALL), MEF2D rearrangements with genes like BCL9, CSF1R, etc., are identified. These rearrangements lead to enhanced MEF2D transcriptional activity, lymphoid transformation, and are associated with a distinct immunophenotype, poor outcome, and sensitivity to histone deacetylase inhibitor treatment [1]. In hepatocellular carcinoma (HCC), MEF2D binds to the promoter region of the CD274 gene (encoding PD-L1), activating its transcription, and thus preventing CD8+ T-cell-mediated antitumor immunity [3]. In gastric cancer, MEF2D promotes liver metastasis by upregulating H1X and downstream target β-CATENIN in response to IL-13 stimulation [5]. However, in breast cancer, knockout of Mef2d in mouse mammary epithelial cells leads to neoplastic transformation, suggesting it may function as a tumor suppressor [6].

In conclusion, Mef2d plays diverse and crucial roles in various biological processes and diseases. Gene knockout models in mice have been instrumental in revealing its role in cancer, including leukemia, HCC, gastric cancer, and breast cancer, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Gu, Zhaohui, Churchman, Michelle, Roberts, Kathryn, Hunger, Stephen P, Mullighan, Charles G. 2016. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia. In Nature communications, 7, 13331. doi:10.1038/ncomms13331. https://pubmed.ncbi.nlm.nih.gov/27824051/

2. Szeto, Aydan C H, Clark, Paula A, Ferreira, Ana C F, Fallon, Padraic G, McKenzie, Andrew N J. 2024. Mef2d potentiates type-2 immune responses and allergic lung inflammation. In Science (New York, N.Y.), 384, eadl0370. doi:10.1126/science.adl0370. https://pubmed.ncbi.nlm.nih.gov/38935708/

3. Xiang, Junyu, Zhang, Ni, Sun, Hui, Liu, Chungang, Qian, Cheng. 2019. Disruption of SIRT7 Increases the Efficacy of Checkpoint Inhibitor via MEF2D Regulation of Programmed Cell Death 1 Ligand 1 in Hepatocellular Carcinoma Cells. In Gastroenterology, 158, 664-678.e24. doi:10.1053/j.gastro.2019.10.025. https://pubmed.ncbi.nlm.nih.gov/31678303/

4. Zhang, Pengcheng, Lu, Rui. . The Molecular and Biological Function of MEF2D in Leukemia. In Advances in experimental medicine and biology, 1459, 379-403. doi:10.1007/978-3-031-62731-6_17. https://pubmed.ncbi.nlm.nih.gov/39017853/

5. Zhang, Yingzi, Lin, Wu, Yang, Yan, Wang, Haiyong, Teng, Lisong. 2024. MEF2D facilitates liver metastasis of gastric cancer cells through directly inducing H1X under IL-13 stimulation. In Cancer letters, 591, 216878. doi:10.1016/j.canlet.2024.216878. https://pubmed.ncbi.nlm.nih.gov/38609001/

6. Wang, Xiaoxia, Shen, He, Chen, Yanmin, Frangou, Costa, Zhang, Jianmin. 2024. MEF2D Functions as a Tumor Suppressor in Breast Cancer. In International journal of molecular sciences, 25, . doi:10.3390/ijms25105207. https://pubmed.ncbi.nlm.nih.gov/38791246/