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Tumor initiation and progression frequently involve oncogenic programs that favor proliferation at the expense of lineage commitment and differentiation. Here, we identify a MYC-driven mechanism that suppresses neuronal identity in glioblastoma (GBM) through repression of the transcription factor aryl hydrocarbon receptor nuclear translocator 2 (ARNT2). ARNT2 is highly expressed in the brain, cerebellum, and iPSC-derived neurons but is markedly reduced in GBM tumors and cell lines, where its loss correlates with higher tumor grade and poor survival. Mechanistically, MYC represses ARNT2 expression, and ARNT2 loss results in reduced expression of neuronal and glial identity genes. Although ARNT2 depletion does not alter GBM cell proliferation in vitro, it significantly enhances tumor growth and lipid metabolic remodeling in vivo. Conversely, ectopic ARNT2 expression suppresses tumor burden in both subcutaneous and orthotopic GBM xenograft models and promotes features of neuronal differentiation. Together, these findings identify ARNT2 as a tumor suppressor in GBM and establish MYC-mediated repression of ARNT2 as a critical mechanism by which GBM maintains a proliferative, undifferentiated, stem-like state.
Pubmed ID: 42063073
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A web-based gene list enrichment analysis tool that provides various types of visualization summaries of collective functions of gene lists. It includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes / proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries.
View all literature mentionsGraph-based alignment of next generation sequencing reads to a population of genomes.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsDatabase of human regulatory elements like enhancers and promoters, and their inferred target genes which is embedded in GeneCards, human gene compendium. Associations between regulatory elements and target genes were based on multiple sources of linking molecular data, along with distance.
View all literature mentionsEnhanced web server for large-scale expression profiling and interactive analysis. GEPIA2 is updated and enhanced version of GEPIA, offering more functionalities, higher resolution data analysis, and additional features like ability to analyze specific cancer subtypes, quantify gene signatures based on single-cell sequencing studies, and allow users to upload their own RNA-seq data for comparison with the TCGA and GTEx datasets; essentially providing more comprehensive and advanced platform for gene expression analysis compared to the original GEPIA version.
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