Rbm10-KO Mouse

Rbm10, an RNA-binding protein, is a key regulator of alternative splicing of primary transcripts. It is involved in multiple cellular processes and is associated with pathways such as the p53-related tumor-suppression pathway. Mutations in Rbm10 can lead to TARP syndrome, an X-linked congenital pleiotropic developmental anomaly, and various cancers, highlighting its biological importance [1,2,3,4].

In an EGFR-driven lung adenocarcinoma (LUAD) mouse model, lung-specific ablation of Rbm10 promoted tumor development, similar to Trp53 ablation. Rbm10 loss led to overlapping gene expression changes enriched in cancer-related pathways and induced key RNA splicing changes in both mice and LUAD patients. Moreover, Rbm10 deficiency conferred high sensitivity to spliceosome inhibition in EGFR-mutated LUAD cells [5]. In thyroid cancer models, loss-of-function Rbm10 mutations, which are enriched in thyroid cancers with distant metastases, increased cell velocity and invasiveness through aberrant splicing of cytoskeletal and extracellular matrix mRNAs, leading to RAC1 activation [6].

In conclusion, Rbm10 plays a crucial role in regulating alternative splicing and is involved in tumor-related biological processes. The study of Rbm10 gene-knockout (KO) or conditional-knockout (CKO) mouse models has revealed its significance in lung and thyroid cancers, providing insights into disease mechanisms and potential therapeutic strategies.

References:

1. Inoue, Akira. 2021. RBM10: Structure, functions, and associated diseases. In Gene, 783, 145463. doi:10.1016/j.gene.2021.145463. https://pubmed.ncbi.nlm.nih.gov/33515724/

2. Jung, Ji Hoon, Lee, Hyemin, Zeng, Shelya X, Lu, Hua. 2020. RBM10, a New Regulator of p53. In Cells, 9, . doi:10.3390/cells9092107. https://pubmed.ncbi.nlm.nih.gov/32947864/

3. Cao, Yingshu, Di, Xin, Zhang, Qinghua, Li, Ranwei, Wang, Ke. 2021. RBM10 Regulates Tumor Apoptosis, Proliferation, and Metastasis. In Frontiers in oncology, 11, 603932. doi:10.3389/fonc.2021.603932. https://pubmed.ncbi.nlm.nih.gov/33718153/

4. Loiselle, Julie J, Sutherland, Leslie C. 2018. RBM10: Harmful or helpful-many factors to consider. In Journal of cellular biochemistry, 119, 3809-3818. doi:10.1002/jcb.26644. https://pubmed.ncbi.nlm.nih.gov/29274279/

5. Bao, Yufang, Zhang, Sirui, Zhang, Xiaoyu, Wang, Zefeng, Wang, Yongbo. . RBM10 Loss Promotes EGFR-Driven Lung Cancer and Confers Sensitivity to Spliceosome Inhibition. In Cancer research, 83, 1490-1502. doi:10.1158/0008-5472.CAN-22-1549. https://pubmed.ncbi.nlm.nih.gov/36853175/

6. Krishnamoorthy, Gnana P, Glover, Anthony R, Untch, Brian R, Bradley, Robert K, Fagin, James A. 2025. RBM10 loss promotes metastases by aberrant splicing of cytoskeletal and extracellular matrix mRNAs. In The Journal of experimental medicine, 222, . doi:10.1084/jem.20241029. https://pubmed.ncbi.nlm.nih.gov/39992626/