Ncoa2, also known as Nuclear receptor coactivator 2, is a member of the Ncoa family of coactivators. It serves as a transcription coactivator, regulating transcription factor activation and inhibition of proteins such as HIF-1α, ARNT, and AhR through protein-protein interactions [4]. Ncoa2 is involved in multiple biological processes and has been associated with pathways like the NF-κB signaling pathway, and hypoxia signaling pathway [3,4].

In various disease models, Ncoa2 has shown distinct functions. In T cells, Ncoa2-deficient mice (Ncoa2fl/fl/CD4Cre) had defective immune responses against implanted MC38 tumors, with reduced tumor-infiltrating CD8+ T cells and IFNγ production, suggesting its role in promoting CD8+ T cell-mediated antitumor immunity by enhancing mitochondrial function via upregulating PGC-1α [2]. In the context of fetal growth restriction (FGR), bioinformatics analysis identified Ncoa2 as a critical gene, with its down-regulation in FGR patients. Overexpression of NcoA2 in HTR-8/SVneo trophoblast cells promoted proliferation, migration, and inhibited apoptosis and pro-inflammatory cytokines secretion via the NF-κB pathway [3]. Also, in a mouse model of mesenchymal chondrosarcoma, introduction of HEY1-NCOA2 into mouse embryonic superficial zone cells induced subcutaneous tumors, showing the role of this fusion in modulating chondrogenic differentiation [1].

In conclusion, Ncoa2 plays essential roles in multiple biological processes and diseases. Its study using gene-knockout mouse models has provided insights into its functions in tumor-immunity, fetal development, and chondrogenic differentiation. Understanding Ncoa2 can potentially offer new therapeutic strategies for related diseases.