Prpf4b, also known as PRP4K, is an essential kinase first identified in fission yeast and evolutionarily conserved. It is a pre-mRNA splicing regulator, phosphorylating spliceosomal components like PRPF6 and PRPF31 during spliceosome B complex formation. It is also involved in pathways such as transcription regulation and the spindle assembly checkpoint, playing an important role in maintaining chromosome stability [4,5].

In cancer research, several studies have implicated Prpf4b. In colon cancer, the phosphorylation level of PRPF4BS431p was significantly correlated with the overall survival of patients, suggesting a role in the disease's prognosis [1]. In lung adenocarcinoma, miR-224 was found to down-regulate PRPF4B, and this miRNA-mRNA pair was associated with lymph node metastasis and prognosis [2]. In hepatocellular carcinoma, miR-371-5p down-regulates PRPF4B, facilitating the G1/S transition and promoting tumor growth [3]. In triple-negative breast cancer, PRPF4B is essential for cancer cell migration and metastasis, and its depletion down-regulates genes in focal adhesion and ECM-interaction pathways [6]. In breast and ovarian cancer, PRP4K (PRPF4B) is a HER2-regulated modifier of taxane sensitivity, with low PRP4K levels correlating with taxane resistance [7]. Also, PRP4K is negatively regulated during epithelial-to-mesenchymal transition, and its depletion in normal mammary cells can increase cell invasion [8].

In conclusion, Prpf4b is crucial for pre-mRNA splicing and participates in multiple cellular pathways. Model-based research, especially in cancer, has shown its significance in tumorigenesis, metastasis, and treatment response. Understanding Prpf4b functions provides insights into disease mechanisms and potential therapeutic targets for various cancers.

References:

1. Gao, Li, Lu, Ying, Chen, Hai-Ning, Zhou, Zong-Guang, Dai, Lunzhi. 2023. Deciphering the Clinical Significance and Kinase Functions of GSK3α in Colon Cancer by Proteomics and Phosphoproteomics. In Molecular & cellular proteomics : MCP, 22, 100545. doi:10.1016/j.mcpro.2023.100545. https://pubmed.ncbi.nlm.nih.gov/37031867/

2. Wang, Yan, Shang, Shengtao, Yu, Kun, Ma, Wenduan, Zhao, Wei. 2020. miR-224, miR-147b and miR-31 associated with lymph node metastasis and prognosis for lung adenocarcinoma by regulating PRPF4B, WDR82 or NR3C2. In PeerJ, 8, e9704. doi:10.7717/peerj.9704. https://pubmed.ncbi.nlm.nih.gov/33282547/

3. Liu, Rui-Yan, Diao, Cai-Feng, Zhang, Yi, Liu, Min, Tang, Hua. 2013. miR-371-5p down-regulates pre mRNA processing factor 4 homolog B (PRPF4B) and facilitates the G1/S transition in human hepatocellular carcinoma cells. In Cancer letters, 335, 351-60. doi:10.1016/j.canlet.2013.02.045. https://pubmed.ncbi.nlm.nih.gov/23466643/

4. Corkery, Dale P, Holly, Alice C, Lahsaee, Sara, Dellaire, Graham. 2015. Connecting the speckles: Splicing kinases and their role in tumorigenesis and treatment response. In Nucleus (Austin, Tex.), 6, 279-88. doi:10.1080/19491034.2015.1062194. https://pubmed.ncbi.nlm.nih.gov/26098145/

5. Habib, Elias B, Mathavarajah, Sabateeshan, Dellaire, Graham. 2022. Tinker, Tailor, Tumour Suppressor: The Many Functions of PRP4K. In Frontiers in genetics, 13, 839963. doi:10.3389/fgene.2022.839963. https://pubmed.ncbi.nlm.nih.gov/35281802/

6. Koedoot, Esmee, Fokkelman, Michiel, Rogkoti, Vasiliki-Maria, Martens, John W M, van de Water, Bob. 2019. Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes. In Nature communications, 10, 2983. doi:10.1038/s41467-019-11020-3. https://pubmed.ncbi.nlm.nih.gov/31278301/

7. Corkery, Dale P, Le Page, Cécile, Meunier, Liliane, Mes-Masson, Anne-Marie, Dellaire, Graham. . PRP4K is a HER2-regulated modifier of taxane sensitivity. In Cell cycle (Georgetown, Tex.), 14, 1059-69. doi:10.1080/15384101.2015.1007775. https://pubmed.ncbi.nlm.nih.gov/25602630/

8. Clarke, Livia E, Cook, Allyson, Mathavarajah, Sabateeshan, Lewis, Stephen M, Dellaire, Graham. . Haploinsufficient tumor suppressor PRP4K is negatively regulated during epithelial-to-mesenchymal transition. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35, e22001. doi:10.1096/fj.202001063R. https://pubmed.ncbi.nlm.nih.gov/34674320/