ZEB2/TWIST1/PRMT5/NuRD Multicomplex Contributes to the Epigenetic Regulation of EMT and Metastasis in Colorectal Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Tissue Samples
2.2. Database of Cancer Patients
2.3. Antibodies and Reagents
2.4. Cell Cultures and Stable Cell Lines
2.5. Western Blotting and Immunoprecipitation
2.6. Mass Spectrometry
2.7. Chromatin Immunoprecipitation Assay
2.8. Quantitative Real-Time PCR
2.9. Luciferase Assay
2.10. Cell Migration and Invasion
2.11. Liver Metastasis Model
2.12. Statistical Analysis
3. Results
3.1. ZEB2 and TWIST1 Are Significantly Upregulated during TGF-β-Induced EMT in CRC Cells and Patient Tissues
3.2. ZEB2 and TWIST1 Contribute to the EMT, Migration, and Invasion Processes in CRC
3.3. ZEB2 Recruits TWIST1 to the Promoter of E-cadherin and Synergistically Represses the Transcription
3.4. ZEB2 Interacts with TWIST1, PRMT5, and NuRD Complex to Form a Functional Multicomplex
3.5. PRMT5 and HDAC2 Are Responsible for the ZEB2-Mediated E-cadherin Repression in CRC
3.6. PRMT5 and HDAC2 Mediate the Migration-, Invasion-, and Metastasis-Promoting Properties of ZEB2
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CRC | colorectal carcinoma |
EMT | epithelial to mesenchymal transition |
NuRD | nucleosome remodeling and deacetylase |
PRMT5 | Protein arginine methyltransferase 5 |
HDAC | Histone deacetylases |
Co-IP | co-immunoprecipitation |
inHDAC2 | Santacruzamate A |
inPRMT5 | GSK3326595 |
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Accession a | Peptide Count b | Confidence Score c | p-Valued d | q-Valued d | Protein Description |
---|---|---|---|---|---|
A0JP08 | 43 (43) | 1595.43 | <0.0001 | <0.0001 | Zinc finger E-box-binding homeobox 2 |
B4DV00 | 5 (5) | 119.52 | <0.0001 | <0.0001 | Protein arginine N-methyltransferase 5 |
Q09028 | 2 (2) | 57.93 | 0.00073 | 0.00169 | Histone-binding protein RBBP4 |
O94776 | 1 (1) | 54.81 | 0.00040 | 0.00025 | Metastasis-associated protein MTA2 |
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Zheng, Y.; Dai, M.; Dong, Y.; Yu, H.; Liu, T.; Feng, X.; Yu, B.; Zhang, H.; Wu, J.; Kong, W.; et al. ZEB2/TWIST1/PRMT5/NuRD Multicomplex Contributes to the Epigenetic Regulation of EMT and Metastasis in Colorectal Carcinoma. Cancers 2022, 14, 3426. https://doi.org/10.3390/cancers14143426
Zheng Y, Dai M, Dong Y, Yu H, Liu T, Feng X, Yu B, Zhang H, Wu J, Kong W, et al. ZEB2/TWIST1/PRMT5/NuRD Multicomplex Contributes to the Epigenetic Regulation of EMT and Metastasis in Colorectal Carcinoma. Cancers. 2022; 14(14):3426. https://doi.org/10.3390/cancers14143426
Chicago/Turabian StyleZheng, Yayuan, Mingrui Dai, Yue Dong, Hanqiao Yu, Tianfu Liu, Xuejian Feng, Bin Yu, Haihong Zhang, Jiaxin Wu, Wei Kong, and et al. 2022. "ZEB2/TWIST1/PRMT5/NuRD Multicomplex Contributes to the Epigenetic Regulation of EMT and Metastasis in Colorectal Carcinoma" Cancers 14, no. 14: 3426. https://doi.org/10.3390/cancers14143426