Usp3, short for Ubiquitin-specific protease 3, is a key deubiquitylation enzyme belonging to the ubiquitin-specific protease family. It plays a critical role in diverse cellular processes such as the DNA damage response, cell cycle regulation, and carcinogenesis, and is involved in pathways like PI3K/AKT [1,2]. Genetic models, especially KO/CKO mouse models, can be valuable for studying its functions.

In osteosarcoma, Usp3 is highly expressed compared to normal bone tissue, and high expression is linked to poor prognosis. Overexpression of Usp3 promotes cell proliferation, migration, and invasion by deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway [1]. In prostate cancer, Usp3 stabilizes and deubiquitinates SMARCA5, promoting DNA damage repair and chemotherapy resistance [3]. In non-small cell lung cancer, high Usp3 expression is associated with advanced pathology stage and poor prognosis, and it accelerates cell proliferation via regulating RBM4 [4]. In breast cancer, USP3 deubiquitinates and stabilizes KLF5, promoting cell proliferation both in vitro and in vivo [5]. In gastric cancer, USP3 promotes progression and metastasis by deubiquitinating and stabilizing COL9A3 and COL6A5 [6].

In conclusion, Usp3 is essential in regulating multiple cellular processes and is involved in the progression of various cancers including osteosarcoma, prostate cancer, non-small cell lung cancer, breast cancer, and gastric cancer. The use of KO/CKO mouse models could potentially further clarify its functions in these disease areas, helping to develop more targeted therapeutic strategies.