the rna-binding ubiquitin ligase mex3a affects glioblastoma tumorigenesis by inducing ubiquitylation and degradation of rig-i

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ID: 156370
2020
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Abstract
Glioblastoma multiforme (GB) is the most malignant primary brain tumor in humans, with an overall survival of approximatively 15 months. The molecular heterogeneity of GB, as well as its rapid progression, invasiveness and the occurrence of drug-resistant cancer stem cells, limits the efficacy of the current treatments. In order to develop an innovative therapeutic strategy, it is mandatory to identify and characterize new molecular players responsible for the GB malignant phenotype. In this study, the RNA-binding ubiquitin ligase MEX3A was selected from a gene expression analysis performed on publicly available datasets, to assess its biological and still-unknown activity in GB tumorigenesis. We find that MEX3A is strongly up-regulated in GB specimens, and this correlates with very low protein levels of RIG-I, a tumor suppressor involved in differentiation, apoptosis and innate immune response. We demonstrate that MEX3A binds RIG-I and induces its ubiquitylation and proteasome-dependent degradation. Further, the genetic depletion of MEX3A leads to an increase of RIG-I protein levels and results in the suppression of GB cell growth. Our findings unveil a novel molecular mechanism involved in GB tumorigenesis and suggest MEX3A and RIG-I as promising therapeutic targets in GB.
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bufalieri2020cancersthe Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Francesca Bufalieri;Miriam Caimano;Ludovica Lospinoso Severini;Irene Basili;Francesco Paglia;Luigi Sampirisi;Elena Loricchio;Marialaura Petroni;Gianluca Canettieri;Antonio Santoro;Luca D’Angelo;Paola Infante;Lucia Di Marcotullio
Journal The Journal of investigative dermatology
Year 2020
DOI
10.3390/cancers12020321
URL
https://www.mdpi.com/2072-6694/12/2/321
Keywords
ubiquitylation Oncology including cancer and carcinogens tumors

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