Rbm6, the RNA-binding motif protein 6, is a known alternative splicing factor with tumor suppressor activity [2,3,4,5,7]. It is involved in regulating mRNA processing and translation. In the context of DNA repair, Rbm6 has been shown to play a role in the homologous recombination (HR) repair pathway, which is crucial for maintaining genome integrity when DNA double-strand breaks (DSBs) occur [1,2].

Rbm6 knockdown leads to a severe reduction in Fe65 protein levels, a positive HR regulator, and consequently impairs HR of DSBs [2]. Also, Rbm6-deficient cancer cells are more sensitive to ATM and PARP inhibition as well as cisplatin [2]. Deletion of the G-patch domain in Rbm6 reduces its interaction with Rad51, resulting in fewer Rad51 foci after ionizing radiation and failure to restore HR integrity, despite no effect on the expression of its splicing targets Fe65 and Eya2 [1]. In laryngocarcinoma and hepatocellular carcinoma, down-regulation of Rbm6 is observed, and over-expression of Rbm6 suppresses cell proliferation, invasion, and promotes apoptosis [3,4]. In contrast, in prostate tumours, Rbm6's role in cell migration is context-dependent, enhancing migration under normal conditions but inhibiting it when ZEB1 is over-expressed [6].

In summary, Rbm6 has diverse functions, mainly acting as a tumor suppressor in many cancer types. Its role in DNA repair through the HR pathway, especially in relation to DSBs, is significant. The study of Rbm6 using gene knockdown models has provided insights into its role in cancer development and response to chemotherapy, suggesting it could be a potential therapeutic target in cancer treatment [1,2,3,4,6].

References:

1. Awwad, Samah W, Darawshe, Malak M, Machour, Feras E, Arman, Inbar, Ayoub, Nabieh. . Recruitment of RBM6 to DNA Double-Strand Breaks Fosters Homologous Recombination Repair. In Molecular and cellular biology, 43, 130-142. doi:10.1080/10985549.2023.2187105. https://pubmed.ncbi.nlm.nih.gov/36941773/

2. Machour, Feras E, Abu-Zhayia, Enas R, Awwad, Samah W, Aqeilan, Rami I, Ayoub, Nabieh. . RBM6 splicing factor promotes homologous recombination repair of double-strand breaks and modulates sensitivity to chemotherapeutic drugs. In Nucleic acids research, 49, 11708-11727. doi:10.1093/nar/gkab976. https://pubmed.ncbi.nlm.nih.gov/34718714/

3. Wang, Qiwei, Wang, Fang, Zhong, Waisheng, Wen, Senli, Chen, Jie. 2019. RNA-binding protein RBM6 as a tumor suppressor gene represses the growth and progression in laryngocarcinoma. In Gene, 697, 26-34. doi:10.1016/j.gene.2019.02.025. https://pubmed.ncbi.nlm.nih.gov/30772516/

4. Ye, Zhihua, Zhang, Junkai, Yang, Yingyu, Li, Lamei, Wang, Xinyi. . RNA-binding protein RBM6 acts as a tumor suppressor gene to inhibit the progression of hepatocellular carcinoma. In Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 26, 402-408. doi:. https://pubmed.ncbi.nlm.nih.gov/34076986/

5. Wang, Ke, Ubriaco, Gino, Sutherland, Leslie C. 2007. RBM6-RBM5 transcription-induced chimeras are differentially expressed in tumours. In BMC genomics, 8, 348. doi:. https://pubmed.ncbi.nlm.nih.gov/17908320/

6. Liu, Ruoyang, Liu, Yu, Zhang, Long, Huang, Zhenlin, Yang, Jinjian. . The Oncopromoting Gene RBM6 Inhibits Prostate Tumour Cell Migration During Epithelial-to-Mesenchymal Transition. In Journal of cellular and molecular medicine, 29, e70397. doi:10.1111/jcmm.70397. https://pubmed.ncbi.nlm.nih.gov/39900560/

7. Peng, Ping, Yin, Qingqing, Sun, Wei, Cheng, Chao, Liu, Dongbo. . Global RNA Interaction and Transcriptome Profiles Demonstrate the Potential Anti-Oncogenic Targets and Pathways of RBM6 in HeLa Cells. In Frontiers in bioscience (Landmark edition), 29, 330. doi:10.31083/j.fbl2909330. https://pubmed.ncbi.nlm.nih.gov/39344314/