SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Clinical Tissue Samples
2.2. Bioinformatics Analysis
2.3. Cell Lines
2.4. DNA Methylation and Gene Expression Analysis
2.5. Plasmids and shRNA Clones
2.6. Assays for Western Blot, Cell Viability, Anchorage-Independent Growth, and Invasion
2.7. Immunofluorescence Staining
2.8. In Vivo Tumor Xenograft and Metastasis Model
2.9. RNA Sequencing Data Analysis
2.10. Chromatin Immunoprecipitation Assay (ChIP Assay)
2.11. Statistical Analysis
3. Results
3.1. Promoter Hypermethylation of SOX1 in Lung Cancer Contributes to SOX1 Silencing/Downregulation
3.2. Ectopic Expression of SOX1 Suppresses Lung Cancer Growth and Invasion
3.3. Restoration of SOX1 Expression Inhibits Tumor Growth and Metastasis in NOD/SCID Mice
3.4. SOX1 Suppresses Lung Cancer Cell Growth and Invasion in an Inducible Expression System
3.5. Signaling Pathways Affected by Inducible Expression of SOX1
3.6. HES1 Is a Direct Target of SOX1
3.7. SOX1 Acts as a Tumor Suppressor by Repressing HES1 in Lung Cancer
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
SOX1 | sex-determining region Y (SRY)-box 1 |
HES1 | hairy and enhancer of split 1 |
NSCLC | non-small-cell lung cancer |
LUAD | lung adenocarcinoma |
LUSC | lung squamous cell carcinoma |
EGFR | epidermal growth factor receptor |
ALK | anaplastic lymphoma kinase |
PD1 | programmed-death 1 |
PDL1 | programmed-death ligand 1 |
RT-PCR | reverse transcription polymerase chain reaction |
MSP | methylation-specific PCR |
CDH1 | E-cadherin |
FN1 | fibronectin |
CDH2 | N-cadherin |
EMT | epithelial–mesenchymal transition |
qRT-PCR | quantitative reverse transcription polymerase chain reaction |
q-MSP | quantitative methylation-specific PCR |
DAC | 5-aza-2′-deoxycytidine |
TSA | trichostatin A |
ChIP | chromatin immunoprecipitation |
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Chang, S.-Y.; Wu, T.-H.; Shih, Y.-L.; Chen, Y.-C.; Su, H.-Y.; Chian, C.-F.; Lin, Y.-W. SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer. Cancers 2023, 15, 2207. https://doi.org/10.3390/cancers15082207
Chang S-Y, Wu T-H, Shih Y-L, Chen Y-C, Su H-Y, Chian C-F, Lin Y-W. SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer. Cancers. 2023; 15(8):2207. https://doi.org/10.3390/cancers15082207
Chicago/Turabian StyleChang, Shan-Yueh, Ti-Hui Wu, Yu-Lueng Shih, Ying-Chieh Chen, Her-Young Su, Chih-Feng Chian, and Ya-Wen Lin. 2023. "SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer" Cancers 15, no. 8: 2207. https://doi.org/10.3390/cancers15082207