Downregulation of the Ubiquitin-E3 Ligase RNF123 Promotes Upregulation of the NF-κB1 Target SerpinE1 in Aggressive Glioblastoma Tumors.

ABSTRACT: This study examined the role of the ubiquitin E3-ligase RNF123 in modulating downstream NF-κB1 targets in glioblastoma (GB) tumor progression. Our findings revealed an oncogenic pathway (miR-155-5p-RNF123-NF-κB1-p50-SerpinE1) that may represent a new therapeutic target pathway for GB patients with isocitrate dehydrogenase 1 and 2 (IDH) WT (wild type). Mechanistically, we demonstrated that RNF123 is downregulated in IDH WT GB patients and leads to the reduction of p50 levels. RNA-sequencing, reverse-phase protein arrays, and in vitro functional assays on IDH WT GB cell lines with RNF123 overexpression showed that SerpinE1 was a downstream target that is negatively regulated by RNF123. SERPINE1 knockdown reduced the proliferation and invasion of IDH

SUBMITTER: Wang X 

PROVIDER: S-EPMC7281601 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature