Nfya, also known as nuclear transcription factor Y subunit alpha, is a transcription factor that plays a crucial role in multiple biological processes. It is involved in pathways related to metabolism, cell proliferation, and development. Nfya is important for coordinating metabolism and proliferation in various cell types, and genetic models are valuable for studying its functions [1,2,3].

In mouse fetal heart development, loss of Nfya in cardiomyocytes leads to altered cell composition, reduced proliferation, and impaired mitochondrial metabolism, resulting in cardiac growth defects and embryonic death. Nfya, interacting with cofactor SP2, activates genes linking metabolism and proliferation at the transcription level [1]. In castration-resistant prostate cancer (CRPC), silencing Nfya in androgen-independent cell lines significantly inhibits cell growth and migration. RNA-seq analysis shows that EGR4 is a downstream target of Nfya, and in vivo studies in mouse models demonstrate that Nfya silencing inhibits xenograft tumor growth [2].

In conclusion, Nfya is essential for regulating prenatal cardiac growth, metabolism, and cell proliferation. Studies using Nfya-deficient mouse models have revealed its role in diseases such as CRPC, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Cui, Miao, Bezprozvannaya, Svetlana, Hao, Tian, Bassel-Duby, Rhonda, Olson, Eric N. 2023. Transcription factor NFYa controls cardiomyocyte metabolism and proliferation during mouse fetal heart development. In Developmental cell, 58, 2867-2880.e7. doi:10.1016/j.devcel.2023.10.012. https://pubmed.ncbi.nlm.nih.gov/37972593/

2. Sun, Guijiang, Shao, Yi, Ma, Qianwang, Wang, Haitao, Shang, Zhiqun. 2024. NFYA-mediated promotion of castration-resistant prostate cancer progression through EGR4 regulation. In Discover oncology, 15, 528. doi:10.1007/s12672-024-01392-4. https://pubmed.ncbi.nlm.nih.gov/39367986/

3. Cui, Miao, Wang, Zhaoning, Chen, Kenian, Bassel-Duby, Rhonda, Olson, Eric N. 2020. Dynamic Transcriptional Responses to Injury of Regenerative and Non-regenerative Cardiomyocytes Revealed by Single-Nucleus RNA Sequencing. In Developmental cell, 53, 102-116.e8. doi:10.1016/j.devcel.2020.02.019. https://pubmed.ncbi.nlm.nih.gov/32220304/