Ncoa3, also known as SRC-3, AIB1, p/CIP, RAC3, ACTR, and TRAM1, is a transcriptional coactivator of NF-κB and other factors [3,4]. It belongs to the p160 nuclear receptor coactivators family and plays a significant role in various biological processes. It is involved in gene transcription regulation, especially in steroid receptor-mediated pathways, and is important for maintaining cell functions and development [1,2].

In multiple cancer types, Ncoa3 has been shown to act as an oncogene. In thyroid cancer, knockdown of Ncoa3 inhibited cell proliferation, invasion, induced cell cycle arrest and apoptosis, while its overexpression promoted these malignant activities through modulating ErbB, AKT, ERK, and β-catenin pathways [4]. In hepatocellular carcinoma, Ncoa3 binds to the TERT promoter, activates TERT expression, and promotes cell growth and tumor progression; knockdown of Ncoa3 suppresses cell viability [5]. In melanoma, downregulation of Ncoa3 expression suppressed melanoma proliferation, increased cell sensitivity to UV radiation, and led to G2-M arrest [6]. In breast cancer-associated adipocytes, high levels of Ncoa3 were associated with a pro-inflammatory profile [3]. Also, in human embryo development, deletion of Ncoa3 delayed development, and it was related to metabolic alterations in oocytes [2].

In conclusion, Ncoa3 is crucial in multiple biological processes and diseases. Its role as an oncogene in various cancers, its impact on human embryo development, and its association with inflammation in breast-related adipocytes are significant findings. Functional studies, especially those using loss-of-function models, have revealed its importance in these areas, providing potential targets for cancer treatment, improvement of assisted reproductive technologies, and understanding of disease-associated inflammation.