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 in inhibiting cell proliferation, migration, and regulating cell cycle progression, acting as a tumor suppressor. It is involved in multiple pathways, such as autophagy, MAPK, and AKT/GSK3β/β-catenin signaling pathways [1,3,5].

In nasopharyngeal carcinoma, MIR106A-5p targets and downregulates Btg3, suppressing autophagy and accelerating the malignant phenotype [1]. In renal cell carcinoma, TRIM65, an E3 ligase, promotes cancer cell proliferation by ubiquitinating and degrading Btg3 [2]. In esophageal adenocarcinoma, Btg3 expression is decreased, and its overexpression suppresses colony formation, proliferation, migration, and invasion of cancer cells [3]. In non-small cell lung cancer, microRNA-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 through 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 the degradation of the viral S2 protein through autophagy and proteasome pathways [7].

In conclusion, Btg3 is a key tumor suppressor gene. Its loss-of-function in various animal models, especially in mouse models, has revealed its significance in tumorigenesis across multiple cancer types, including nasopharyngeal, renal, esophageal, lung, ovarian, and skin cancers. Additionally, it also plays a role in antiviral defense mechanisms against porcine epidemic diarrhea virus [1,2,3,4,5,6,7].