{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies in medulloblastoma models have revealed that piggyBac transposable element‐derived 5 (PGBD5) functions as a tumor mutator whose ectopic activation, especially in the context of aberrant Sonic Hedgehog (SHH) signaling, drives the transformation of cerebellar granule cell progenitors. PGBD5 promotes tumor development by inducing distinct DNA repair and neurodevelopmental factor expression, resulting in a cell state that is particularly susceptible to oncogenic alterations. This transposase‐like activity is implicated in fostering a genomic environment conducive to tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n \n \nIn addition, PGBD5-mediated genomic rearrangements in medulloblastoma are characterized by the presence of specific sequence breakpoints that recurrently disrupt known tumor suppressor genes and oncogenes. These structural DNA alterations provide a mechanistic explanation for the oncogenic transformation observed in childhood medulloblastomas, further supporting the role of PGBD5 as a mutator enzyme in these tumors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n \n \nFurther extending its oncogenic influence, recent investigations in glioma have demonstrated that elevated PGBD5 expression is closely linked with enhanced cell migration, invasion, and proliferation. In glioma tissue and cell models, silencing PGBD5 not only inhibited these malignant properties by triggering apoptosis and causing cell cycle arrest at the G2/M phase but also attenuated tumor growth in vivo, with evidence indicating that these effects are mediated via modulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Makiko Yamada, Ross R Keller, Rodrigo Lopez Gutierrez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Childhood cancer mutagenesis caused by transposase-derived PGBD5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Adv (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/sciadv.adn4649"}], "href": "https://doi.org/10.1126/sciadv.adn4649"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38517960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38517960"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Pengren Luo, Jinhong Yang, Lipeng Jian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of PGBD5 inhibits the malignant progression of glioma through upregulation of the PPAR pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2024.5643"}], "href": "https://doi.org/10.3892/ijo.2024.5643"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38577941"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38577941"}]}]}]}