The Multiple Faces of the MRN Complex: Roles in Medulloblastoma and Beyond

Author:

Petroni Marialaura12ORCID,La Monica Veronica1ORCID,Fabretti Francesca1,Augusto Mariaconcetta13,Battaglini Damiana1,Polonara Francesca12,Di Giulio Stefano1,Giannini Giuseppe12ORCID

Affiliation:

1. Department of Molecular Medicine, University La Sapienza, 00161 Rome, Italy

2. Istituto Pasteur-Fondazione Cenci Bolognetti, 00161 Rome, Italy

3. Center for Life Nano- & Neuro-Science, Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy

Abstract

Hypomorphic mutations in MRN complex genes are frequently found in cancer, supporting their role as oncosuppressors. However, unlike canonical oncosuppressors, MRN proteins are often overexpressed in tumor tissues, where they actively work to counteract DSBs induced by both oncogene-dependent RS and radio-chemotherapy. Moreover, at the same time, MRN genes are also essential genes, since the constitutive KO of each component leads to embryonic lethality. Therefore, even though it is paradoxical, MRN genes may work as oncosuppressive, oncopromoting, and essential genes. In this review, we discussed how alterations in the MRN complex impact the physiopathology of cancer, in light of our recent discoveries on the gene–dosage-dependent effect of NBS1 in Medulloblastoma. These updates aim to understand whether MRN complex can be realistically used as a prognostic/predictive marker and/or as a therapeutic target for the treatment of cancer patients in the future.

Funder

Associazione Italiana per la ricerca sul cancro

Fondi Ricerca Ateneo La Sapienza

PNRR-Rome Technopole FP7

PNRR-PE6-Spoke4

Italian Ministry of Education-Universities and Research- Dipartimenti di Eccellenza

Istituto Pasteur-Fondazione Cenci Bolognetti

Fondazione Telethon—Italy

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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