CSIG-07. GAIN-OF-FUNCTION MUTANT P53 REGULATES LONG-NONCODING RNAS IN GLIOBLASTOMA

Abstract P53 is frequently mutated in most human cancers, including glioblastoma (GBM). Many p53 mutants acquire gain-of-function oncogenic effects through only partially understood mechanisms. To investigate the role of mutant (MUT-p53) GBM, we performed ChIP-seq wildtype (WT-p53) and MUT-p53 GBM cell lines. Among 2834 unique peaks reads cells, found 242 long non-coding RNAs (lncRNAs) with up to 145 fold enrichment relative WT-p53. LncRNAs regulate many molecular cellular functions, gene expression, proliferation, death, cancer stem renewal differentiation. We selected lncRNAs SOX21-AS1 LINC00643 highly enriched binding by investigated their expressions functions pathway. ChIP confirmation promoters these lncRNAs. that are deregulated correlated patient survival TCGA database. LncRNAs, knocked down siRNA, significant death induced si-SOX21-AS1, but not si-LINC00643. Overexpression cells led inhibition migration, invasion vivo xenograft growth. mediated MUT-p53. Co-expression its mouse homologous a RCAS transgenic model reduced tumor growth improved animal survival. elucidate mechanisms action lncRNA, Chromatin Isolation RNA purification high-throughput sequencing (CHIRP-seq) identify targets. binds HIF1a 5’ promoter/enhancer region. at hypoxia condition mRNA protein expression. Our study shows for first time regulates subset mediate GBM.