{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Zhang Y"],"funding":["NINDS NIH HHS","NCI NIH HHS"],"pubmed_abstract":["Gain-of-function mutations of p53 (GOF-MUT-p53) act as oncogenes by regulating gene transcription. We screened for the genome-wide transcriptional targets of GOF-MUT-p53 in glioblastoma (GBM) and found that a significant subset of them were long non-coding RNAs (lncRNA). Among these, LINC00643 was strongly repressed by GOF-MUT-p53 but not wild-type p53. LINC00643 was downregulated in GBM and low-grade glioma and correlated with patient survival. LINC00643 and its conserved third exon (Exon3) suppressed GBM cell proliferation, migration, invasion, stem cell self-renewal, and in vivo tumor growth Mechanistically, ChIRP-seq identified HIF1α as a key LINC00643 interactor. Under hypoxia, LINC00643 repressed HIF1α expression and its target genes by interacting with the HIF1α enhancer. Knockdown of GOF-MUT-p53 upregulated LINC00643 and reduces HIF1α, revealing a regulatory axis. These findings show extensive regulation of lncRNAs by GOF-MUT-p53 and uncover a novel mechanism by which GOF-MUT-p53 drives GBM through repression of LINC00643 and dysregulation of the HIF1α pathway."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.09.16.676559"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12458236"],"repository":["biostudies-literature"],"pubmed_title":["Gain-of-function mutant p53 regulates long-noncoding RNA LINC00643 to modulate HIF1α in glioblastoma."],"pmcid":["PMC12458236"],"funding_grant_id":["R21 NS122136","R01 NS122222","U01 CA220841","P30 CA044579"],"pubmed_authors":["Abounader R","Reon B","Sun Y","Holland E","Grello C","Dube CJ","Yuan F","Saha S","Marcinkiewicz P","Zhang Y","Dutta A","Gibert MK","Chief D","Hudson K"],"additional_accession":[]},"is_claimable":false,"name":"Gain-of-function mutant p53 regulates long-noncoding RNA LINC00643 to modulate HIF1α in glioblastoma.","description":"Gain-of-function mutations of p53 (GOF-MUT-p53) act as oncogenes by regulating gene transcription. We screened for the genome-wide transcriptional targets of GOF-MUT-p53 in glioblastoma (GBM) and found that a significant subset of them were long non-coding RNAs (lncRNA). Among these, LINC00643 was strongly repressed by GOF-MUT-p53 but not wild-type p53. LINC00643 was downregulated in GBM and low-grade glioma and correlated with patient survival. LINC00643 and its conserved third exon (Exon3) suppressed GBM cell proliferation, migration, invasion, stem cell self-renewal, and in vivo tumor growth Mechanistically, ChIRP-seq identified HIF1α as a key LINC00643 interactor. Under hypoxia, LINC00643 repressed HIF1α expression and its target genes by interacting with the HIF1α enhancer. Knockdown of GOF-MUT-p53 upregulated LINC00643 and reduces HIF1α, revealing a regulatory axis. These findings show extensive regulation of lncRNAs by GOF-MUT-p53 and uncover a novel mechanism by which GOF-MUT-p53 drives GBM through repression of LINC00643 and dysregulation of the HIF1α pathway.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-05-02T03:18:11.85Z","creation":"2026-05-02T03:09:59.555Z"},"accession":"S-EPMC12458236","cross_references":{"pubmed":["41000845"],"doi":["10.1101/2025.09.16.676559"]}}