Srpk1-KO Mouse

Srpk1, or Serine-Arginine Protein Kinase 1, is an enzyme that phosphorylates serine/arginine-rich splicing factors, playing a crucial role in alternative splicing, a process implicated in many biological functions [1,2,3,6]. It is involved in multiple signaling pathways such as PI3K/AKT, NF-κB, and TGF-β, which are associated with oncogenesis [1]. Srpk1 also has functions in cell cycle progression, innate immune response, chromatin reorganization, and germ cell development [2].

In the context of cancer, elevated Srpk1 expression is correlated with advanced disease stage and poor survival in many epithelial-derived cancers. In pre-clinical studies, increased Srpk1 expression was associated with cancer cell proliferation, invasion, migration, apoptosis in vitro, as well as tumor growth, tumorigenicity, and metastasis in vivo [1]. For instance, in colon cancer, Srpk1 overexpression enhanced the anti-apoptosis ability of cancer cells under oxaliplatin treatment, and it was found to enhance IKK kinase and IκB phosphorylation to promote NF-κB nuclear translocation, conferring oxaliplatin resistance [7]. In non-small-cell lung cancer, high Srpk1 expression was significantly associated with poor progression-free survival in patients undergoing gefitinib treatment, and Srpk1 promoted gefitinib resistance by activating the Wnt pathway [5]. In lung adenocarcinoma, N6-methyladenosine-modified Srpk1 promoted aerobic glycolysis via PKM splicing [4].

In conclusion, Srpk1 is a key regulator in alternative splicing and is involved in multiple signaling pathways related to oncogenesis. Studies, often through in vitro and in vivo pre-clinical models (functionally equivalent to gene-based research models), have shown its significant role in cancer development, drug resistance, and progression, suggesting it could be a potential therapeutic target in cancer treatment [1,4,5,6,7].

References:

1. Duggan, William P, O'Connell, Emer, Prehn, Jochen H M, Burke, John P. 2022. Serine-Arginine Protein Kinase 1 (SRPK1): a systematic review of its multimodal role in oncogenesis. In Molecular and cellular biochemistry, 477, 2451-2467. doi:10.1007/s11010-022-04456-7. https://pubmed.ncbi.nlm.nih.gov/35583632/

2. Patel, Mitesh, Sachidanandan, Manojkumar, Adnan, Mohd. 2018. Serine arginine protein kinase 1 (SRPK1): a moonlighting protein with theranostic ability in cancer prevention. In Molecular biology reports, 46, 1487-1497. doi:10.1007/s11033-018-4545-5. https://pubmed.ncbi.nlm.nih.gov/30535769/

3. Aubol, Brandon E, Adams, Joseph A. 2022. SRPK1 regulates RNA binding in a pre-spliceosomal complex using a catalytic bypass mechanism. In The FEBS journal, 289, 7428-7445. doi:10.1111/febs.16560. https://pubmed.ncbi.nlm.nih.gov/35730996/

4. Wang, Anqi, Zeng, Yuanyuan, Zhang, Weijie, Liu, Zeyi, Huang, Jian-An. 2024. N6-methyladenosine-modified SRPK1 promotes aerobic glycolysis of lung adenocarcinoma via PKM splicing. In Cellular & molecular biology letters, 29, 106. doi:10.1186/s11658-024-00622-5. https://pubmed.ncbi.nlm.nih.gov/39095708/

5. Huang, Jing-Qiang, Duan, Ling-Xin, Liu, Qiu-Yu, Xu, Xingzhi, Gong, Li-Yun. 2023. Serine-arginine protein kinase 1 (SRPK1) promotes EGFR-TKI resistance by enhancing GSK3β Ser9 autophosphorylation independent of its kinase activity in non-small-cell lung cancer. In Oncogene, 42, 1233-1246. doi:10.1038/s41388-023-02645-2. https://pubmed.ncbi.nlm.nih.gov/36869126/

6. Nikas, Ilias P, Themistocleous, Sophie C, Paschou, Stavroula A, Tsamis, Konstantinos I, Ryu, Han Suk. 2019. Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives. In Cells, 9, . doi:10.3390/cells9010019. https://pubmed.ncbi.nlm.nih.gov/31861708/

7. Huang, Jing-Qiang, Li, He-Feng, Zhu, Jing, Wang, Liang, Gong, Li-Yun. 2021. SRPK1/AKT axis promotes oxaliplatin-induced anti-apoptosis via NF-κB activation in colon cancer. In Journal of translational medicine, 19, 280. doi:10.1186/s12967-021-02954-8. https://pubmed.ncbi.nlm.nih.gov/34193174/