Roles Of FOXM1Transcription Factor In Response To Oxidative Stress

Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system’s ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. p53is a tumour suppressor, the amount and transcriptional activity of p53is regulated by post-translational modification, such as phosphorylaion, sumoylation and acetylation. While p53levels are kept low in unteated cells, they rapidly increase in response to stressors, such as DNA damage. On one hand, p53drive activation of cell cycle checkpoint pathways to arrest cell cycle progression to provide adequate time to repair DNA damage. On the other hand, p53is a endounuclease itself, it plays a role in DNA repairing.FOXM1is a transcription factor of the Forkhead family. It plays important roles in the control of cellular proliferation, senescence, DNA repair, regeneration, and tumor progression. In this study, By detecting the expression of DNA damage makers and comet assay, we established oxidative stress models induced by UV and H2O2. In adittion, we constructed FOXM1RNA interference lentivirus vector in vitro, and both of lentivirus that express FOXM1or interfere FOXM1have been successfully collected. In the model of oxidative stress induced by UV, Western blot was adopted to observe the FOXM1protein expression, and result in the increased expression of FOXM1. Therfefore, we assume that FOXM1is essential in oxidative stress. Comet assay showed that the tail moment of DNA oxidative damage is incresed in osteosarcoma cells inferfered with FOXM1. Further more, we detected the mRNA expressin of DNA damage makers by Real-time quantitative Polymerase Chain Reaction. We found that PARP1, which is a important polymerases recruited in response to DNA damage by base excision repair, and ATR mRNA were up-regulated with FOXM1interference. Altogether, these results demonstrate that FOXM1may be involved in oxidative stress by regulating expression of PARP1and ATR. Our results suggest a critical involvement of FOXM1in response to oxidative DNA damage.