Depletion of DNA Polymerase Theta Inhibits Tumor Growth and Promotes Genome Instability through the cGAS-STING-ISG Pathway in Esophageal Squamous Cell Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Clinical Specimens
2.2. RNA Sequence Analysis
2.3. Cell Lines
2.4. Plasmids and Lentivirus Preparation and Infection
2.5. RNA Isolation and Real-Time Quantitative Polymerase Chain Reaction
2.6. Protein Extraction and Western Blot Analysis
2.7. MTT Assay Following Genotoxic Drug Treatments
2.8. Colony Formation Assay
2.9. Ionizing Radiation
2.10. Immunofluorescence (IF) Staining and Confocal Microscopy
2.11. Single Cell Gel Electrophoresis Assay (Comet Assay)
2.12. Enzyme-Linked Immunosorbent Assay (ELISA)
2.13. In Vivo Tumorigenicity Assay
2.14. Statistical Analysis
3. Results
3.1. POLQ Is Upregulated in ESCC and Correlates with Unfavorable Clinical Outcome
3.2. POLQ Maintains Genome Stability in ESCC Cells
3.3. POLQ Depletion Sensitizes ESCC Cells to Mutiple Genotoxic Agents
3.4. Double Knockout POLQ and FANCD2 Drastically Inhibits ESCC Growth Both In Vivo and In Vitro
3.5. Double Knockout of POLQ and FANCD2 Significantly Induces Genome Instability and the Formation of Micronuclei
3.6. Double Knockout POLQ and FANCD2 Induces the Expression of Interferon-Stimulated Genes (ISGs) and Upregulates cGAS and STAT1 Phosphorylation
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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Li, J.; Ko, J.M.-Y.; Dai, W.; Yu, V.Z.; Ng, H.Y.; Hoffmann, J.-S.; Lung, M.L. Depletion of DNA Polymerase Theta Inhibits Tumor Growth and Promotes Genome Instability through the cGAS-STING-ISG Pathway in Esophageal Squamous Cell Carcinoma. Cancers 2021, 13, 3204. https://doi.org/10.3390/cancers13133204
Li J, Ko JM-Y, Dai W, Yu VZ, Ng HY, Hoffmann J-S, Lung ML. Depletion of DNA Polymerase Theta Inhibits Tumor Growth and Promotes Genome Instability through the cGAS-STING-ISG Pathway in Esophageal Squamous Cell Carcinoma. Cancers. 2021; 13(13):3204. https://doi.org/10.3390/cancers13133204
Chicago/Turabian StyleLi, Jian, Josephine Mun-Yee Ko, Wei Dai, Valen Zhuoyou Yu, Hoi Yan Ng, Jean-Sébastien Hoffmann, and Maria Li Lung. 2021. "Depletion of DNA Polymerase Theta Inhibits Tumor Growth and Promotes Genome Instability through the cGAS-STING-ISG Pathway in Esophageal Squamous Cell Carcinoma" Cancers 13, no. 13: 3204. https://doi.org/10.3390/cancers13133204