Nuclear receptor NR5A2 negatively regulates cell proliferation and tumor growth in nervous system malignancies.
Animals
Cell Cycle
/ physiology
Cell Line, Tumor
Cell Proliferation
Glioblastoma
/ drug therapy
Humans
Kaplan-Meier Estimate
Mice, SCID
Nervous System Neoplasms
/ drug therapy
Neural Stem Cells
/ drug effects
Neuroblastoma
/ metabolism
Phosphatidylcholines
/ pharmacology
Receptors, Cytoplasmic and Nuclear
/ agonists
Xenograft Model Antitumor Assays
LRH1
agonists
glioblastoma
neuroblastoma
proliferation
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
28 09 2021
28 09 2021
Historique:
accepted:
09
08
2021
entrez:
25
9
2021
pubmed:
26
9
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
Nervous system malignancies are characterized by rapid progression and poor survival rates. These clinical observations underscore the need for novel therapeutic insights and pharmacological targets. To this end, here, we identify the orphan nuclear receptor NR5A2/LRH1 as a negative regulator of cancer cell proliferation and promising pharmacological target for nervous system-related tumors. In particular, clinical data from publicly available databases suggest that high expression levels of NR5A2 are associated with favorable prognosis in patients with glioblastoma and neuroblastoma tumors. Consistently, we experimentally show that NR5A2 is sufficient to strongly suppress proliferation of both human and mouse glioblastoma and neuroblastoma cells without inducing apoptosis. Moreover, short hairpin RNA-mediated knockdown of the basal expression levels of NR5A2 in glioblastoma cells promotes their cell cycle progression. The antiproliferative effect of NR5A2 is mediated by the transcriptional induction of negative regulators of the cell cycle,
Identifiants
pubmed: 34561301
pii: 2015243118
doi: 10.1073/pnas.2015243118
pmc: PMC8488649
pii:
doi:
Substances chimiques
NR5A2 protein, human
0
Phosphatidylcholines
0
Receptors, Cytoplasmic and Nuclear
0
1,2-dilauroylphosphatidylcholine
18285-71-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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