Chromatin Remodelling Molecule ARID1A Determines Metastatic Heterogeneity in Triple-Negative Breast Cancer by Competitively Binding to YAP
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Samples
2.2. Cell Lines and Cell Culture
2.3. Lentiviral shRNA Production, Infection and Knockdown of Genes
Species | Gene | Sequences |
mouse | ARID1AKO-1 | 5′-GGTCCCTGTTGTTGCGAGTA-3′ |
mouse | ARID1AKO-2 | 5′-gACCCCATGACCATGCAGGGC-3′ |
mouse | YAPKD-1 | 5′-AGGCCAGTACTGATGCAGGTA-3′ |
mouse | YAPKD-2 | 5′-CAGGACCTCTTCCTGATGGAT-3′ |
human | ARID1AKO-1 | 5′-CACCGATGGTCATCGGGTACCGCTG-3′ |
human | ARID1AKO-2 | 5′-CACCGCCCCTCAATGACCTCCAGTA-3′ |
human | ARID1AOE-1 | 5′-CACCGGGCGCTCTAGCCGCTCAGTC-3′ |
human | ARID1AOE-2 | 5′-CACCGCTTGGGTCGAGGCTGCTGCG-3′ |
human | YAPKD-1 | 5′-CCCAGTTAAATGTTCACCAAT-3′ |
human | YAPKD-2 | 5′-CACCAAGCTAGATAAAGAA-3′ |
2.4. Cellular Fractionation, Western Blot and Co-IP Assay
2.5. Preparation of RNA and Quantitative Real-Time PCR
2.6. RNA-Seq Library Construction and Analysis
2.7. Wound Healing Assay
2.8. Transwell Migration and Invasion Assays
2.9. Immunofluorescent Staining
2.10. In Vivo Tumour Metastasis Model
2.11. Immunohistochemical Analysis
2.12. Hematoxylin/Eosin Staining
2.13. Statistical Analysis
3. Results
3.1. ARID1A-Low Expression Associated with Metastasis and Poor Prognosis in TNBC
3.2. Inhibition of ARID1A Promotes Migration and Invasion in TNBC Cells
3.3. ARID1A Inhibits TNBC Metastasis In Vivo
3.4. ARID1A Regulates EMT in TNBC
3.5. YAP and Hippo Pathway Involved in ARID1A-Regulated EMT and Tumour Metastasis
3.6. ARID1A Competitively Binds YAP to Form ARID1A/YAP Complex
3.7. ARID1A Combined with YAP via the WW Domain
3.8. ARID1A and YAP Co-Regulate Tumour Metastasis In Vivo
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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Wang, Y.; Chen, X.; Qiao, X.; Xie, Y.; Guo, D.; Li, B.; Cao, J.; Tao, Z.; Hu, X. Chromatin Remodelling Molecule ARID1A Determines Metastatic Heterogeneity in Triple-Negative Breast Cancer by Competitively Binding to YAP. Cancers 2023, 15, 2447. https://doi.org/10.3390/cancers15092447
Wang Y, Chen X, Qiao X, Xie Y, Guo D, Li B, Cao J, Tao Z, Hu X. Chromatin Remodelling Molecule ARID1A Determines Metastatic Heterogeneity in Triple-Negative Breast Cancer by Competitively Binding to YAP. Cancers. 2023; 15(9):2447. https://doi.org/10.3390/cancers15092447
Chicago/Turabian StyleWang, Ye, Xinyu Chen, Xiaosu Qiao, Yizhao Xie, Duancheng Guo, Bin Li, Jianing Cao, Zhonghua Tao, and Xichun Hu. 2023. "Chromatin Remodelling Molecule ARID1A Determines Metastatic Heterogeneity in Triple-Negative Breast Cancer by Competitively Binding to YAP" Cancers 15, no. 9: 2447. https://doi.org/10.3390/cancers15092447