BRAF/EZH2 Signaling Represses miR-129-5p Inhibition of SOX4 Thereby Modulating BRAFi Resistance in Melanoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Data Sets
2.2. Cell Culture
2.3. miRNA Detection by Quantitative Real-Time PCR
2.4. Transcriptional Analysis by qRT-PCR
2.5. DNA Constructs and siRNA
2.6. Transfections
2.7. Immunoblot Snalyses
2.8. Cell Viability Assay
2.9. Cell Growth Assay
2.10. Cell Cycle Analysis
2.11. 3D Spheroid Growth Assay
2.12. Luciferase Reporter Assay
2.13. Statistical Analyses
3. Results
3.1. Expression of miR-129-5p Increases during BRAFi and MEKi Treatment
3.2. miR-129-5p Expression Decreases During Emergence of Resistance to BRAFi
3.3. EZH2 Suppresses miR-129-5p Expression Downstream of Constitutive Active BRAF Signaling
3.4. miR-129-5p Acts as Tumor Suppressor In Vitro and in a 3D Spheroid Model
3.5. SOX4 is a Targeted by miR-129-5p During BRAFi Response
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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Gebhardt, K.; Edemir, B.; Groß, E.; Nemetschke, L.; Kewitz-Hempel, S.; Moritz, R.K.C.; Sunderkötter, C.; Gerloff, D. BRAF/EZH2 Signaling Represses miR-129-5p Inhibition of SOX4 Thereby Modulating BRAFi Resistance in Melanoma. Cancers 2021, 13, 2393. https://doi.org/10.3390/cancers13102393
Gebhardt K, Edemir B, Groß E, Nemetschke L, Kewitz-Hempel S, Moritz RKC, Sunderkötter C, Gerloff D. BRAF/EZH2 Signaling Represses miR-129-5p Inhibition of SOX4 Thereby Modulating BRAFi Resistance in Melanoma. Cancers. 2021; 13(10):2393. https://doi.org/10.3390/cancers13102393
Chicago/Turabian StyleGebhardt, Kathleen, Bayram Edemir, Elisabeth Groß, Linda Nemetschke, Stefanie Kewitz-Hempel, Rose K. C. Moritz, Cord Sunderkötter, and Dennis Gerloff. 2021. "BRAF/EZH2 Signaling Represses miR-129-5p Inhibition of SOX4 Thereby Modulating BRAFi Resistance in Melanoma" Cancers 13, no. 10: 2393. https://doi.org/10.3390/cancers13102393