ADAR2 Protein Is Associated with Overall Survival in GBM Patients and Its Decrease Triggers the Anchorage-Independent Cell Growth Signature

Valeriana Cesarini; Domenico Alessandro Silvestris; Federica Galeano; Valentina Tassinari; Maurizio Martini; Franco Locatelli; Angela Gallo

doi:10.3390/biom12081142

ADAR2 Protein Is Associated with Overall Survival in GBM Patients and Its Decrease Triggers the Anchorage-Independent Cell Growth Signature

Biomolecules. 2022 Aug 19;12(8):1142. doi: 10.3390/biom12081142.

Authors

Valeriana Cesarini^{1

2}, Domenico Alessandro Silvestris¹, Federica Galeano¹, Valentina Tassinari^{1

3}, Maurizio Martini^{4

5}, Franco Locatelli^{1

6}, Angela Gallo¹

Affiliations

¹ Department of Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, 00146 Rome, Italy.
² Department of Biomedical Sciences, Institute of Translational Pharmacology, National Research Council of Italy (CNR), 00133 Rome, Italy.
³ Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy.
⁴ Pathology of the Adult and Developmental Age "Gaetano Barresi", Università di Messina, 98125 Messina, Italy.
⁵ Department of Life Sciences and Public Health, Policlinico "A. Gemelli", IRCCS, Catholic University of Sacred Heart, 00168 Rome, Italy.
⁶ Department of Gynecology/Obstetrics and Pediatrics, Sapienza University of Rome, 00161 Rome, Italy.

Abstract

Background: Epitranscriptomic mechanisms, such as A-to-I RNA editing mediated by ADAR deaminases, contribute to cancer heterogeneity and patients' stratification. ADAR enzymes can change the sequence, structure, and expression of several RNAs, affecting cancer cell behavior. In glioblastoma, an overall decrease in ADAR2 RNA level/activity has been reported. However, no data on ADAR2 protein levels in GBM patient tissues are available; and most data are based on ADARs overexpression experiments.

Methods: We performed IHC analysis on GBM tissues and correlated ADAR2 levels and patients' overall survival. We silenced ADAR2 in GBM cells, studied cell behavior, and performed a gene expression/editing analysis.

Results: GBM tissues do not all show a low/no ADAR2 level, as expected by previous studies. Although, different amounts of ADAR2 protein were observed in different patients, with a low level correlating with a poor patient outcome. Indeed, reducing the endogenous ADAR2 protein in GBM cells promotes cell proliferation and migration and changes the cell's program to an anchorage-independent growth mode. In addition, deep-seq data and bioinformatics analysis indicated multiple RNAs are differently expressed/edited upon siADAR2.

Conclusion: ADAR2 protein is an important deaminase in GBM and its amount correlates with patient prognosis.

Keywords: ADAM12; ADAR2; PTPX3; RNA editing; anchorage-independent growth; cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Deaminase* / genetics
Adenosine Deaminase* / metabolism
Cell Proliferation
Glioblastoma* / genetics
Humans
RNA Editing
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism

Substances

RNA-Binding Proteins
Adenosine Deaminase

Grants and funding

This work was supported by the AIRC (Associazione Italiana Ricerca sul Cancro) IG grants (n. 13202) to A.G. and by the Mia Neri Foundation e Cassa di Sovvenzioni e Risparmio fra il Personale della Banca d’Italia to A.G.