PUF60, also known as poly(U)-binding splicing factor 60, is a nucleic acid-binding protein involved in multiple nuclear processes such as pre-mRNA splicing, apoptosis, and transcription regulation [4]. It is essential for embryonic development and has been linked to various biological pathways and diseases [2,4,7]. Genetic models, like KO or CKO mouse models, can potentially be used to further explore its functions.

PUF60 has been shown to promote the mitotic cell cycle and cancer progression. In lung adenocarcinoma, elevated copy number and expression of PUF60 are related to poor prognosis. PUF60 depletion inhibits cell-cycle G2/M transition, cell proliferation, and tumor development by causing exon skipping in genes like CDC25C [1]. In glioblastoma, PUF60 is highly expressed and knockdown decreases cell proliferation. It reduces the ubiquitination level of EGFR by regulating STUB1, activating the EGFR-AKT pathway [3]. In breast cancer, PUF60 is highly expressed and accelerates cancer progression by down-regulating PTEN expression [5]. In bladder cancer, PUF60 expression is higher in tumor tissues, and it promotes tumor progression through the PUF60/AURKA axis [6]. In ovarian cancer, PUF60 is highly expressed, and its silencing enhances the stability of mRNA transcripts involved in oxidative phosphorylation, preventing tumor progression [8].

In conclusion, PUF60 is crucial for embryonic development and plays significant roles in regulating the cell cycle and cancer progression. Model-based research, especially KO/CKO mouse models if available, could further clarify its functions in these processes. Its dysregulation is associated with various cancers, highlighting its potential as a therapeutic target in oncology research [1,3,5,6,8].

References:

1. Xu, Nan, Ren, Yunpeng, Bao, Yufang, Xie, Gangcai, Wang, Yongbo. 2023. PUF60 promotes cell cycle and lung cancer progression by regulating alternative splicing of CDC25C. In Cell reports, 42, 113041. doi:10.1016/j.celrep.2023.113041. https://pubmed.ncbi.nlm.nih.gov/37682709/

2. Hoogenboom, Amarens, Falix, Farah A, van der Laan, Liselot, Sadikovic, Bekim, van Haelst, Mieke M. 2024. Novel PUF60 variant suggesting an interaction between Verheij and Cornelia de Lange syndrome: phenotype description and review of the literature. In European journal of human genetics : EJHG, 32, 435-439. doi:10.1038/s41431-023-01527-1. https://pubmed.ncbi.nlm.nih.gov/38273166/

3. Wang, Fang, Peng, Lan, Sun, Yikui, Zhang, Burong, Lu, Shuaijun. 2022. PUF60 promotes glioblastoma progression through regulation of EGFR stability. In Biochemical and biophysical research communications, 636, 190-196. doi:10.1016/j.bbrc.2022.10.082. https://pubmed.ncbi.nlm.nih.gov/36335869/

4. Bach, Michal Yacobi, Miron, Sivan Reytan, Kurolap, Alina, Feldman, Hagit Baris. 2024. PUF60 loss-of-function with normal cognition should be considered in the differential diagnosis of Klippel-Feil syndrome. In American journal of medical genetics. Part A, 194, e63550. doi:10.1002/ajmg.a.63550. https://pubmed.ncbi.nlm.nih.gov/38297485/

5. Sun, Dongying, Lei, Wei, Hou, Xiaodong, Li, Hui, Ni, Wenlu. 2019. PUF60 accelerates the progression of breast cancer through downregulation of PTEN expression. In Cancer management and research, 11, 821-830. doi:10.2147/CMAR.S180242. https://pubmed.ncbi.nlm.nih.gov/30697074/

6. Long, Qian, An, Xin, Chen, Miao, Zheng, Fufu, He, Liru. 2020. PUF60/AURKA Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer. In Frontiers in oncology, 10, 568015. doi:10.3389/fonc.2020.568015. https://pubmed.ncbi.nlm.nih.gov/33117697/

7. Baum, Emily, Huang, Wenming, Vincent-Delorme, Catherine, Antebi, Adam, Dafsari, Hormos Salimi. 2024. Novel Genetic and Phenotypic Expansion in Ameliorated PUF60-Related Disorders. In International journal of molecular sciences, 25, . doi:10.3390/ijms25042053. https://pubmed.ncbi.nlm.nih.gov/38396730/

8. Zhang, Cancan, Ni, Xiaoge, Tao, Chunlin, Wu, Zhiyong, Zhang, Rong. 2023. Targeting PUF60 prevents tumor progression by retarding mRNA decay of oxidative phosphorylation in ovarian cancer. In Cellular oncology (Dordrecht, Netherlands), 47, 157-174. doi:10.1007/s13402-023-00859-w. https://pubmed.ncbi.nlm.nih.gov/37632669/