EWSR1-WT1 Target Genes and Therapeutic Options Identified in a Novel DSRCT In Vitro Model
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient-Derived DSRCT Specimen
2.2. Cell Culture
2.3. Single-Cell RNA Sequencing
2.4. Comparison R2 Dataset
2.5. Introduction of shRNAs into OV-054 DSRCT Cells
2.6. RNA Isolation, PCR, and qPCR
2.7. RNA Sequencing
2.8. Time-Lapse Imaging and Particle Analysis
2.9. Medium-Throughput Compound Screen
2.10. UNC2025 Screen
3. Results
3.1. Establishment and Characterization of a DSRCT In Vitro Preclinical Model
3.2. shRNAs Targeting the EWSR1-WT Breakpoint Create an Effective Knock-Down of the Fusion mRNA
3.3. EWSR1-WT1 Expression Affects Cell Shape, Cell Propagation, and the Transcriptome
3.4. Drug Screen on OV-054 Cells Reveals Effective Compounds Targeting RTKs and Downstream Pathways
3.5. MERTK, Regulated by EWSR1-WT1, Is a Potential Therapeutic Target in DSRCT
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Bleijs, M.; Pleijte, C.; Engels, S.; Ringnalda, F.; Meyer-Wentrup, F.; van de Wetering, M.; Clevers, H. EWSR1-WT1 Target Genes and Therapeutic Options Identified in a Novel DSRCT In Vitro Model. Cancers 2021, 13, 6072. https://doi.org/10.3390/cancers13236072
Bleijs M, Pleijte C, Engels S, Ringnalda F, Meyer-Wentrup F, van de Wetering M, Clevers H. EWSR1-WT1 Target Genes and Therapeutic Options Identified in a Novel DSRCT In Vitro Model. Cancers. 2021; 13(23):6072. https://doi.org/10.3390/cancers13236072
Chicago/Turabian StyleBleijs, Margit, Corine Pleijte, Sem Engels, Femke Ringnalda, Friederike Meyer-Wentrup, Marc van de Wetering, and Hans Clevers. 2021. "EWSR1-WT1 Target Genes and Therapeutic Options Identified in a Novel DSRCT In Vitro Model" Cancers 13, no. 23: 6072. https://doi.org/10.3390/cancers13236072