Otud6a, short for Ovarian tumor deubiquitinase 6A, is a deubiquitinating enzyme. It plays crucial roles in multiple biological processes by regulating the stability of various proteins, thus being involved in pathways like the Hippo signaling pathway, innate immune response, and cell cycle regulation [3,4,7]. Its dysregulation is associated with several diseases including inflammatory bowel disease (IBD), multiple types of cancers, and cardiac hypertrophy, highlighting its biological importance. Gene knockout (KO) and conditional knockout (CKO) mouse models have been valuable in studying its functions [1,2,5,6,8].

In KO mouse models, Otud6a deficiency attenuated DSS or TNBS-induced colitis and AOM/DSS-induced colitis-related colon cancer, indicating its role in promoting intestinal inflammation and colitis [1]. CKO mice were less prone to BCa tumorigenesis induced by BBN, suggesting OTUD6A-CDC6 axis promotes tumour progression [2]. Genetic ablation of OTUD6A in mice repressed prostatic tumorigenesis, showing its role in prostate cancer [5]. OTUD6A oligonucleotides suppressed prostate tumorigenesis in PtenPC-/-mice and patient-derived xenograft (PDX) models, highlighting its significance in prostate cancer [6]. In OTUD6a gene knockout mice, TAC-or Ang II-induced ventricular hypertrophy and dysfunction were attenuated, revealing its role in cardiac inflammation and hypertrophy [8].

In conclusion, Otud6a is a key deubiquitinase involved in diverse biological functions. Through KO and CKO mouse models, its roles in IBD, various cancers, and cardiac hypertrophy have been well-demonstrated. These findings provide potential therapeutic targets for treating related diseases.