Pluto Bioinformatics

GSE60530: Profile of gene expression in U87-MG xenografts expressing control vector (V0), the ubiquitin ligase KPC1 or the p50 subunit of the NF-kB transcription factor, using RNASeq analysis of transcripts mapped independently to the human and murine genomes

Bulk RNA sequencing

Purpose: We identified KPC1 as the ubiquitin ligase that binds to the p105 precursor of NF-kB, ubiquitinates it and mediates its proteasomal processing to generate the p50 active subunit of the transcription factor. Using U87-MG human glioblastoma xenografts, we observed that overexpression of KPC1 results in strong inhibition of tumor growth mediated via excessive generation of p50.The goal of this RNASeq study was to analyze the profile of gene expression in xenografts overexpressing control (V0), KPC1 or p50 vectors, and to further understand how the altered gene expression patterns can explain the tumor suppressive effect we observed.; Results:Transcript analysis of U87-MG xenografts overexpressing control (V0), KPC1 or p50 vector mapped to the human genome revealed:; A strong similarity between overexpression of p50 and KPC1 (correlation of 0.51, p-value<10-300 ); A specific signature of NF-kB targets [21 of the consistently changed genes are known to be regulated by NF-kB (p-value<3.410-9 )]; A significant (p-value<1.410-18) increase in the expression of 40 tumor suppressor genes, with no significant change in other classes.; A significant down regulation of a cluster of genes including LIN28B, IL-6, HMAGA2 and VEGFA. This finding links well to an established regulatory axis involving LIN28B, Let-7 microRNA, and IL-6 in inflammation and cell transformation that is regulated by NF-kB.; SOURCE: Aaron Ciechanover (aaroncie@tx.technion.ac.il) - Technion-Israel Institute of Technology