Settayanon Sirapat, Chanvorachote Pithi, Mutirangura Apiwat
Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Interdisciplinary Program of Biomedical Sciences, Graduate School, Chulalongkorn University, Bangkok, Thailand.
Sci Rep. 2025 Jan 25;15(1):3215. doi: 10.1038/s41598-025-87773-3.
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.
一种理想的化学治疗剂能够损伤DNA，特别是癌细胞中的DNA，而不损害正常细胞。最近，我们使用HMGB1质粒的A盒作为分子剪刀在正常细胞中产生DNA缺口。DNA缺口缓解了DNA张力并增强了DNA强度，从而防止DNA双链断裂（DSB）。由于癌症中由HMGB1产生的DNA缺口的形成可能与正常细胞不同，因此将A盒引入癌细胞的结果可能会有所不同。我们证明，在肺癌细胞中，A盒会产生γH2AX焦点和与DSB相关的组蛋白修饰。我们将A盒质粒转染到肺癌细胞系中以过表达A盒，并评估γH2AX焦点和其他DNA损伤反应（DDR）信号级联标志物（包括ATM、ATR和p53）的表达水平。然后，我们证明了DSB对肺癌的下游影响，即降低细胞增殖、减少细胞迁移并促进细胞凋亡。因此，肺癌中的A盒通过破坏癌症DNA产生了与正常细胞相反的结果。
