Fbxo25, an F-box protein, is a component of the SCF protein E3 ubiquitin ligase complex. It binds to substrates specifically, regulating multiple biological processes and pathways. For example, it is involved in MAPK signaling pathway regulation [2]. It also has significance in ubiquitination-related protein quality control, cellular signalings, and cell differentiation, especially in cardiac tissue [3]. Genetic models like gene knockout (KO) mouse models can be valuable for studying its functions.

In cutaneous squamous cell carcinoma (cSCC), stable silencing of Fbxo25 in SCC13 cells led to reduced tumor growth, with down-regulation of cyclin D1, indicating Fbxo25 promotes cSCC growth and metastasis through cyclin D1 [1]. In NSCLC, interference of Fbxo25 could significantly inhibit cell proliferation, invasion, and migration in H1299 cells, suggesting its role in promoting the tumorigenicity of lung cancer cells [4]. In cardiomyocyte development, silencing endogenous Fbxo25 increased Tbx5 and Nkx2-5 mRNA levels and suppressed mESC-derived cardiomyocyte differentiation, while exogenous expression of FBXO25 down-regulated NKX2-5 level in human ESC-derived cardiomyocytes [3]. In B cell lymphoma, monoallelic loss of Fbxo25 and stabilizing HAX1 phosphodegron mutations were identified, and knockdown of Fbxo25 significantly accelerated lymphoma development in Eμ-Myc mice and in a human MCL xenotransplant model, suggesting Fbxo25 functions as a haploinsufficient tumor suppressor [5].

In conclusion, Fbxo25 has diverse functions, regulating cell growth, metastasis in cancer, and cardiomyocyte development. KO/CKO mouse models have contributed to understanding its roles in diseases such as cSCC, NSCLC, and lymphoma, providing insights into potential therapeutic targets and disease mechanisms.