The role of Box A of HMGB1 in producing γH2AX associated DNA breaks in lung cancer
Abstract An ideal chemotherapeutic agent damages DNA, specifically in cancer cells, without harming normal cells. Recently, we used Box A of HMGB1 plasmid as molecular scissors to produce DNA gaps in normal cells. The DNA gap relieves DNA tension and increases DNA strength, preventing DNA double-str...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-87773-3 |
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| author | Sirapat Settayanon Pithi Chanvorachote Apiwat Mutirangura |
| author_facet | Sirapat Settayanon Pithi Chanvorachote Apiwat Mutirangura |
| author_sort | Sirapat Settayanon |
| collection | DOAJ |
| description | Abstract An ideal chemotherapeutic agent damages DNA, specifically in cancer cells, without harming normal cells. Recently, we used Box A of HMGB1 plasmid as molecular scissors to produce DNA gaps in normal cells. The DNA gap relieves DNA tension and increases DNA strength, preventing DNA double-strand breaks (DSBs). Since the formation of HMGB1-produced DNA gaps in cancers may differ from normal cells, the outcome of introducing Box A into cancer cells may be different. We demonstrated that in lung cancer cells, γH2AX foci and histone modification associating DSBs were produced by Box A. We transfected Box A plasmid into lung cancer cell lines to overexpress Box A and evaluated the expression levels of γH2AX foci and other DNA damage response (DDR) signaling cascade markers, including ATM, ATR, and p53. Then, we demonstrated the downstream effects of DSBs on lung cancer, lowering cell proliferation, decreasing cell migration, and promoting apoptosis. Thus, Box A in lung cancer promoted the opposite outcome to normal cells by breaking cancer DNA. |
| format | Article |
| id | doaj-art-44e741d53aa5423fae6162aa9acef929 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-44e741d53aa5423fae6162aa9acef9292025-01-26T12:32:51ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-87773-3The role of Box A of HMGB1 in producing γH2AX associated DNA breaks in lung cancerSirapat Settayanon0Pithi Chanvorachote1Apiwat Mutirangura2Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial HospitalCell-Based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn UniversityCenter of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial HospitalAbstract An ideal chemotherapeutic agent damages DNA, specifically in cancer cells, without harming normal cells. Recently, we used Box A of HMGB1 plasmid as molecular scissors to produce DNA gaps in normal cells. The DNA gap relieves DNA tension and increases DNA strength, preventing DNA double-strand breaks (DSBs). Since the formation of HMGB1-produced DNA gaps in cancers may differ from normal cells, the outcome of introducing Box A into cancer cells may be different. We demonstrated that in lung cancer cells, γH2AX foci and histone modification associating DSBs were produced by Box A. We transfected Box A plasmid into lung cancer cell lines to overexpress Box A and evaluated the expression levels of γH2AX foci and other DNA damage response (DDR) signaling cascade markers, including ATM, ATR, and p53. Then, we demonstrated the downstream effects of DSBs on lung cancer, lowering cell proliferation, decreasing cell migration, and promoting apoptosis. Thus, Box A in lung cancer promoted the opposite outcome to normal cells by breaking cancer DNA.https://doi.org/10.1038/s41598-025-87773-3Lung cancerBox A of HMGB1DNA double-strand breaksYouth-DNA-gapDNA damage responseγH2AX |
| spellingShingle | Sirapat Settayanon Pithi Chanvorachote Apiwat Mutirangura The role of Box A of HMGB1 in producing γH2AX associated DNA breaks in lung cancer Scientific Reports Lung cancer Box A of HMGB1 DNA double-strand breaks Youth-DNA-gap DNA damage response γH2AX |
| title | The role of Box A of HMGB1 in producing γH2AX associated DNA breaks in lung cancer |
| title_full | The role of Box A of HMGB1 in producing γH2AX associated DNA breaks in lung cancer |
| title_fullStr | The role of Box A of HMGB1 in producing γH2AX associated DNA breaks in lung cancer |
| title_full_unstemmed | The role of Box A of HMGB1 in producing γH2AX associated DNA breaks in lung cancer |
| title_short | The role of Box A of HMGB1 in producing γH2AX associated DNA breaks in lung cancer |
| title_sort | role of box a of hmgb1 in producing γh2ax associated dna breaks in lung cancer |
| topic | Lung cancer Box A of HMGB1 DNA double-strand breaks Youth-DNA-gap DNA damage response γH2AX |
| url | https://doi.org/10.1038/s41598-025-87773-3 |
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