ADAR2 Protein Is Associated with Overall Survival in GBM Patients and Its Decrease Triggers the Anchorage-Independent Cell Growth Signature.
ADAM12
ADAR2
PTPX3
RNA editing
anchorage-independent growth
cancer
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
19 08 2022
19 08 2022
Historique:
received:
22
09
2021
revised:
14
06
2022
accepted:
15
08
2022
entrez:
26
8
2022
pubmed:
27
8
2022
medline:
30
8
2022
Statut:
epublish
Résumé
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. 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. 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. ADAR2 protein is an important deaminase in GBM and its amount correlates with patient prognosis.
Sections du résumé
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.
Identifiants
pubmed: 36009036
pii: biom12081142
doi: 10.3390/biom12081142
pmc: PMC9405742
pii:
doi:
Substances chimiques
RNA-Binding Proteins
0
Adenosine Deaminase
EC 3.5.4.4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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