Rbm39, or RNA-binding motif protein 39, is an RNA-binding protein involved in transcriptional co-regulation and alternative RNA splicing. It has been associated with multiple biological processes and is emerging as a significant factor in cancer-related pathways [1].

Loss-of-function experiments have demonstrated its importance in various cancer types. For example, depletion of Rbm39 in cholangiocarcinoma cells using CRISPR/Cas9 or shRNA inhibited cell proliferation in vitro and tumor growth in mice, and revealed a novel Rbm39-EZH2-β-catenin signaling axis crucial for CCA growth [2]. In T-cell acute lymphoblastic leukemia, knockdown of Rbm39 restricted cell proliferation both in vitro and in vivo, and indisulam, which induces Rbm39 degradation, caused widespread aberrant splicing of downstream effector proteins like THOC1 [3]. In osteosarcoma, pharmacological depletion of Rbm39 by aryl sulfonamide (E7820) repressed tumor growth and sensitized cells to cisplatin treatment [4].

In conclusion, Rbm39 is a key protein in RNA-related regulatory processes. Model-based research, especially loss-of-function experiments in cancer models, has shown its significant role in promoting tumor growth and metastasis in multiple cancer types, highlighting its potential as a therapeutic target.