Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
Department of Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
Comput Biol Med. 2024 Sep;180:108776. doi: 10.1016/j.compbiomed.2024.108776. Epub 2024 Jul 31.
Inflammatory response is a crucial factor that affects prognosis and therapeutic effect in tumor cells. Although some studies have shown that inflammation could make DNA more vulnerable to external attacks, resulting in serious DNA damage, the underlying mechanism remains unknown. Then, using tumor necrosis factor α (TNF-α) and lipopolysaccharide (LPS), this research elevated the level of inflammation in cancer cells, and hydrogen peroxide (HO) and ultraviolet (UV) were utilized as common reactive oxygen species (ROS)-induced DNA damage agents. We show that either HO or UV achieved a more substantial antiproliferative effect in the inflammation environment compared with HO or UV treatment alone. The inflammation environment enhanced HO- or UV-induced cell apoptosis and ROS production. Although the phenomenon that inflammation itself could trigger ROS-dependent DNA damage was well known, the underlying mechanism for the sensitization of inflammation to trigger intense DNA damage via ROS in cancer cells remains unclear. In this study, the inflammation-related genes and the corresponding expression information were obtained from the TCGA and fetched genes associated with inflammatory factors. Screening of thirteen inflammatory-related, including ATM, and prognostic genes. In addition, KEGG analysis of prognostic genes shows that biological processes such as DNA replication. ATM and ATR, which belong to the PI3/PI4-kinase family, can activate p53. Inflammation promotes the vulnerability of DNA by activating the ATM/ATR/p53 pathway, while not affecting the DNA damage repair pathway. In brief, this research suggested that inflammation made DNA vulnerable due to the amplifying HO- or UV-induced ROS production and the motoring ATM/ATR/p53 pathway. In addition, our findings revealed that inflammation's motoring of the ATM/ATR/p53 pathway plays a crucial role in DNA damage. Therefore, exploring the mechanism between inflammation and ROS-dependent DNA damage would be extremely valuable and innovative. This study would somewhat establish a better understanding of inflammation, DNA damage, and cancer.
炎症反应是影响肿瘤细胞预后和治疗效果的关键因素。虽然一些研究表明炎症可以使 DNA 更容易受到外部攻击，导致严重的 DNA 损伤，但潜在的机制仍不清楚。然后，本研究使用肿瘤坏死因子 α（TNF-α）和脂多糖（LPS）来提高癌细胞的炎症水平，并利用过氧化氢（HO）和紫外线（UV）作为常见的活性氧（ROS）诱导的 DNA 损伤剂。我们发现，无论是 HO 还是 UV，在炎症环境中的抗增殖效果都明显优于单独的 HO 或 UV 处理。炎症环境增强了 HO 或 UV 诱导的细胞凋亡和 ROS 产生。虽然炎症本身可以引发 ROS 依赖性 DNA 损伤的现象是众所周知的，但炎症通过 ROS 来增强对癌症细胞中强烈 DNA 损伤的敏感性的潜在机制尚不清楚。在这项研究中，从 TCGA 获得了与炎症相关的基因及其相应的表达信息，并获取了与炎症因子相关的基因。筛选出十三种与炎症相关的基因，包括 ATM，并进行预后基因分析。此外，预后基因的 KEGG 分析表明，DNA 复制等生物学过程。ATM 和 ATR 属于 PI3/PI4-激酶家族，可以激活 p53。炎症通过激活 ATM/ATR/p53 通路促进 DNA 的易损性，而不影响 DNA 损伤修复通路。简而言之，这项研究表明，炎症通过激活 ATM/ATR/p53 通路来增加 HO 或 UV 诱导的 ROS 产生，从而使 DNA 变得脆弱。此外，我们的研究结果表明，炎症对 ATM/ATR/p53 通路的驱动作用在 DNA 损伤中起着关键作用。因此，探索炎症与 ROS 依赖性 DNA 损伤之间的机制将具有极高的价值和创新性。本研究将在一定程度上更好地理解炎症、DNA 损伤和癌症。
