The RNA-Binding Ubiquitin Ligase MEX3A Affects Glioblastoma Tumorigenesis by Inducing Ubiquitylation and Degradation of RIG-I.

Cancers (Basel) 2020 Jan 30;12(2). Epub 2020 Jan 30.

Department of Molecular Medicine, Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy.

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.

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12020321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072305PMC
January 2020

Publication Analysis

Top Keywords

protein levels
8
ubiquitin ligase
8
ligase mex3a
8
rna-binding ubiquitin
8
mex3a
6
rig-i
5
malignant phenotype
4
phenotype study
4
genetic depletion
4
study rna-binding
4
responsible malignant
4
players responsible
4
selected gene
4
ubiquitylation proteasome-dependent
4
expression analysis
4
gene expression
4
proteasome-dependent degradation
4
mex3a selected
4
depletion mex3a
4
degradation genetic
4

Similar Publications