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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 06, 2018 |
| Title |
gene expression when silencing RBMS3 in ovarain cancer cell line SKOV3 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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).
Experimental design: Fluorescence in situ hybridization and immunochemistry 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 in vitro, and by intraperitoneal tumor model in vivo. The mechanism by which RBMS3 loss sustained activation of miR-126-5p/β-catenin/CBP signaling and the effects of RBMS3 and miR-126-5p competitively regulating DKK3, AXIN1, BACH1 and NFAT5 was explored using CLIP-seq (PRJNA484809), RIP, electrophoretic mobility shift and immunoblotting immunofluorescence assays.
Results: 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 in vitro and in vivo. RBMS3 inhibited β-catenin/CBP signaling through directly associating with and stabilizing multiple negative regulators, including DKK3, AXIN1, BACH1 and NFAT5, via competitively preventing the miR-126-5p-mediated repression of these transcripts. Importantly, co-therapy of CBP/β-catenin antagonist PRI-724 induced sensitization of RBMS3-deleted EOC to platinum therapy.
Conclusions: 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.
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| Overall design |
Gene expression in ovarian cancer cell line SKOV3 was measured in control cells and RBMS3 KO cells. Two independent experiments were performed for each experiment.
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| Contributor(s) |
Wu G |
| Citation missing |
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| Submission date |
Nov 05, 2018 |
| Last update date |
Nov 20, 2018 |
| Contact name |
Geyan Wu |
| E-mail(s) |
noreason2004@163.com
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| Organization name |
Sun Yet-sen universtiy
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| Street address |
Zhongshan Er Road
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510080 |
| Country |
China |
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| Platforms (1) |
| GPL21185 |
Agilent-072363 SurePrint G3 Human GE v3 8x60K Microarray 039494 [Probe Name Version] |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA503831 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE122146_RAW.tar |
49.5 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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