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Open AccessArticle

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

1
Department of Molecular Medicine, Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy
2
Dipartimento di Neurologia e Psichiatria, Neurochirurgia, Sapienza University, Viale dell’Università 30, 00185 Rome, Italy
3
Center for Life Nano Science ([email protected]), Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy
4
Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti-Department of Molecular Medicine, Sapienza University, Viale Regina Elena 291, 00161 Rome, Italy
*
Authors to whom correspondence should be addressed.
These authors equally contributed to the work.
Cancers 2020, 12(2), 321; https://doi.org/10.3390/cancers12020321
Received: 23 December 2019 / Revised: 24 January 2020 / Accepted: 28 January 2020 / Published: 30 January 2020
(This article belongs to the Special Issue Tumors of the Central Nervous System: An Update)
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. View Full-Text
Keywords: glioblastoma multiforme (GB); ubiquitylation; E3-ligase; MEX3A; RIG-I glioblastoma multiforme (GB); ubiquitylation; E3-ligase; MEX3A; RIG-I
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Bufalieri, F.; Caimano, M.; Lospinoso Severini, L.; Basili, I.; Paglia, F.; Sampirisi, L.; Loricchio, E.; Petroni, M.; Canettieri, G.; Santoro, A.; D’Angelo, L.; Infante, P.; Di Marcotullio, L. The RNA-Binding Ubiquitin Ligase MEX3A Affects Glioblastoma Tumorigenesis by Inducing Ubiquitylation and Degradation of RIG-I. Cancers 2020, 12, 321.

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