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.

The rna-binding ubiquitin ligase mex3a affects glioblastoma tumorigenesis by inducing ubiquitylation and degradation of rig-i / Bufalieri, F.; Caimano, M.; Severini, L. L.; Basili, I.; Paglia, F.; Sampirisi, L.; Loricchio, E.; Petroni, M.; Canettieri, G.; Santoro, A.; D'Angelo, L.; Infante, P.; Di Marcotullio, L.. - In: CANCERS. - ISSN 2072-6694. - 12:2(2020), p. 321. [10.3390/cancers12020321]

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

Bufalieri F.
Primo
;
Caimano M.;Basili I.;Paglia F.;Sampirisi L.;Loricchio E.;Petroni M.;Canettieri G.;Santoro A.;Infante P.;Di Marcotullio L.
2020

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.
2020
E3-ligase; Glioblastoma multiforme (GB); MEX3A; RIG-I; Ubiquitylation
01 Pubblicazione su rivista::01a Articolo in rivista
The rna-binding ubiquitin ligase mex3a affects glioblastoma tumorigenesis by inducing ubiquitylation and degradation of rig-i / Bufalieri, F.; Caimano, M.; Severini, L. L.; Basili, I.; Paglia, F.; Sampirisi, L.; Loricchio, E.; Petroni, M.; Canettieri, G.; Santoro, A.; D'Angelo, L.; Infante, P.; Di Marcotullio, L.. - In: CANCERS. - ISSN 2072-6694. - 12:2(2020), p. 321. [10.3390/cancers12020321]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1384478
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