Loss of RBMS3 Confers Platinum Resistance in Epithelial Ovarian Cancer via Activation of miR-126-5p/β-catenin/CBP signaling.
Animals
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Bridged Bicyclo Compounds, Heterocyclic
/ administration & dosage
Carcinoma, Ovarian Epithelial
/ drug therapy
Cisplatin
/ administration & dosage
Drug Resistance, Neoplasm
/ genetics
Female
Gene Deletion
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Kaplan-Meier Estimate
Mice, Inbred NOD
Mice, Knockout
Mice, SCID
MicroRNAs
/ genetics
Peptide Fragments
/ genetics
Pyrimidinones
/ administration & dosage
RNA-Binding Proteins
/ genetics
Sialoglycoproteins
/ genetics
Signal Transduction
/ drug effects
Trans-Activators
/ genetics
Xenograft Model Antitumor Assays
beta Catenin
/ genetics
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 02 2019
01 02 2019
Historique:
received:
07
08
2018
revised:
24
09
2018
accepted:
27
09
2018
pubmed:
4
10
2018
medline:
14
4
2020
entrez:
4
10
2018
Statut:
ppublish
Résumé
The development of resistance to platinum-based chemotherapy remains the unsurmountable obstacle in cancer treatment and consequently leads to tumor relapse. This study aims to investigate the mechanism by which loss of RBMS3 induced chemoresistance in epithelial ovarian cancer (EOC). FISH and IHC were used to determine deletion frequency and expression of RBMS3 in 15 clinical EOC tissues and 150 clinicopathologically characterized EOC specimens. The effects of RBMS3 deletion and CBP/β-catenin antagonist PRI-724 in chemoresistance were examined by clone formation and Annexin V assays Loss of RBMS3 in EOC was correlated with the overall and relapse-free survival. Genetic ablation of RBMS3 significantly enhanced, whereas restoration of RBMS3 reduced, the chemoresistance ability of EOC cells both Our results demonstrate that genetic ablation of RBMS3 contributes to chemoresistance and PRI-724 may serve as a potential tailored treatment for patients with RBMS3-deleted EOC.
Identifiants
pubmed: 30279231
pii: 1078-0432.CCR-18-2554
doi: 10.1158/1078-0432.CCR-18-2554
doi:
Substances chimiques
Bridged Bicyclo Compounds, Heterocyclic
0
ICG 001
0
MIRN126 microRNA, human
0
MicroRNAs
0
Peptide Fragments
0
Pyrimidinones
0
RBMS3 protein, human
0
RNA-Binding Proteins
0
Sialoglycoproteins
0
Trans-Activators
0
beta Catenin
0
bone sialoprotein (35-62), human
0
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1022-1035Informations de copyright
©2018 American Association for Cancer Research.