{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUTP25 – which in zebrafish is encoded by the def gene and in humans is known as DIEXF – plays a critical role during organogenesis by ensuring proper digestive organ development. In zebrafish, loss‐of‐function mutations in def lead to hypoplastic digestive organs, a defect accompanied by a selective up‐regulation of the Delta113p53 isoform that subsequently triggers cell cycle arrest without promoting apoptosis. This tissue‐specific regulatory interplay highlights the importance of UTP25/DIEXF in balancing proliferative signals during early organ formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in organogenesis, UTP25/DEF functions as a nucleolar factor that is indispensable for ribosome biogenesis. It participates in pre‐ribosomal RNA processing as a component of the small ribosomal subunit processome. Deficiency or haploinsufficiency of DEF disrupts normal ribosome assembly, compromises the development of the peripheral sympathetic nervous system, and has been shown to decrease the tumor growth rate in a MYCN‐driven neuroblastoma model. In human neuroblastoma cell lines, depletion of this factor induces apoptosis, suggesting that DEF/UTP25 represents a potential vulnerability in tumor cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComplementary studies further underscore the intricate regulation of genes controlling digestive organ development. Investigations into Hirschsprung’s disease have examined the roles of regulatory microRNAs such as miR-195 in gut motility disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, a genome-wide epigenetic study identified an Alu repeat element (AluSq2) with differential methylation located upstream of the DIEXF promoter, indicating that epigenetic modifications may directly influence DIEXF transcript diversity and protein expression. This differential regulation in both normal and cancer tissue contexts points to the broader significance of UTP25/DIEXF alterations in human disease, including potential roles as a tumor biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jun Chen, Hua Ruan, Sok Meng Ng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of function of def selectively up-regulates Delta113p53 expression to arrest expansion growth of digestive organs in zebrafish."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1366405"}], "href": "https://doi.org/10.1101/gad.1366405"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16322560"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16322560"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "T Tao, S B Sondalle, H Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The pre-rRNA processing factor DEF is rate limiting for the pathogenesis of MYCN-driven neuroblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2016.527"}], "href": "https://doi.org/10.1038/onc.2016.527"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28263972"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28263972"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hao Lei, Junwei Tang, Hongxing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-195 affects cell migration and cell proliferation by down-regulating DIEXF in Hirschsprung's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Gastroenterol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-230X-14-123"}], "href": "https://doi.org/10.1186/1471-230X-14-123"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25007945"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25007945"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Berta Martín, Stella Pappa, Anna Díez-Villanueva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tissue and cancer-specific expression of DIEXF is epigenetically mediated by an Alu repeat."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epigenetics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15592294.2020.1722398"}], "href": "https://doi.org/10.1080/15592294.2020.1722398"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32041475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32041475"}]}]}]}