Btg3, also known as BTG anti-proliferation factor 3, is a member of the antiproliferative BTG gene family and a downstream target of p53. It plays a crucial role as a tumor suppressor, influencing various cellular processes such as cell proliferation, apoptosis, and autophagy. It is also involved in regulating the tumor microenvironment and angiogenesis. Genetic models, like knockout mouse models, can be valuable for studying its functions.

In nasopharyngeal carcinoma, MIR106A-5p targets Btg3 to suppress autophagy and accelerate the malignant phenotype [1]. In renal cell carcinoma, TRIM65 promotes cell proliferation by ubiquitinating and degrading Btg3 [2]. In esophageal adenocarcinoma, decreased Btg3 expression is associated with lymph node metastases, and its overexpression suppresses cell colony formation, proliferation, migration, and invasion [3]. In non-small cell lung cancer, miR-20b-5p promotes cell proliferation and migration by targeting Btg3 [4]. In epithelial ovarian cancer, Btg3 overexpression inhibits cell proliferation and invasion and promotes apoptosis by regulating the AKT/GSK3β/β-catenin signaling pathway [5]. In skin carcinogenesis, Btg3 knockout in mice augmented papilloma development as BTG3-knockout keratinocytes promoted adipocyte differentiation, which in turn promoted keratinocyte migration [6]. In porcine epidemic diarrhea virus infection, Btg3 inhibits viral replication by promoting degradation of the viral S2 protein through autophagy and proteasome pathways [7].

In conclusion, Btg3 functions as a significant tumor suppressor in multiple cancer types. Its absence or down-regulation often leads to enhanced cancer cell proliferation, invasion, and metastasis, as well as disrupted cellular processes. The study of Btg3 knockout mouse models has provided valuable insights into its role in cancer development, offering potential targets for cancer therapy.