RNF2, also known as Ring1B or Ring2, is a member of the Ring finger protein family and functions as an E3 ubiquitin ligase for monoubiquitination of histone H2A at lysine 119 (H2AK119ub). It is involved in multiple cellular signaling pathways, such as the Wnt/ß -catenin pathway [4]. RNF2 has been implicated in various biological processes and diseases, especially cancer [1].

In cancer research, RNF2 has been shown to play oncogenic roles. In hepatocellular carcinoma, it promotes metastasis via enhancing epithelial-mesenchymal transition (EMT) by repressing E-Cadherin transcription [2]. In colon cancer, RNF2 promotes tumor growth by regulating the ubiquitination and degradation of IRF4 [5]. In chondrosarcoma, RNF2 fosters progression by elevating CBX7 degradation via the ubiquitination pathway [6]. Deleting genes encoding RNF2 in syngeneic murine models of triple-negative breast cancer can induce durable tumor rejection and establish immune memory by enhancing the infiltration and activation of natural killer and CD4+ T cells [3].

In conclusion, RNF2 is a crucial E3 ubiquitin ligase involved in histone modification and multiple signaling pathways. Its study, especially through gene-knockout mouse models, has revealed its significant roles in cancer progression and the tumor-immune microenvironment, providing potential targets for cancer treatment.