Autophagy and GG-NER in UVB-induced skin cancer - Admin Supplement

UVB 诱导的皮肤癌中的自噬和 GG-NER - 管理补充

• 批准号: 9791591
• 负责人: Yu-Ying He
• 金额: $ 16.2万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9791591
• 关键词: Affect; Autophagocytosis; Binding; Brain; Chemicals; Chronic; Clustered Regularly Interspaced Short Palindromic Repeats; DNA Damage; Data; Diet; Dietary Supplementation; Genome; Goals; Human; Incidence; Knowledge; Lung; Malignant Neoplasms; Messenger RNA; Methyltransferase; MicroRNAs; Modification; Molecular; Mus; Mutation; Nuclear; Oncogenic; Pathway interactions; RNA; RNA Stability; RNA methylation; RNA-Protein Interaction; Regulation; Risk Factors; Role; Skin; Skin Cancer; Skin Neoplasms; Sunlight; Supplementation; Testing; Translations; Tumor Suppression; UVB induced; Ultraviolet B Radiation; Untranslated RNA; Vitamin E; Work; dietary supplements; global genomic repair; irradiation; knock-down; novel; parent grant; prevent; skin cancer prevention; tumor; tumorigenesis; tumorigenic; vitamin E succinate

Abstract The primary goal of the proposed supplement is to determine the mechanism by which dietary supplementation with a vitamin E derivative protects against UVB-induced skin cancer, which is within the scope of the parent grant. The incidence of skin cancer, the most common cancer in the US, continues to rise at an alarming rate. One major risk factor is UVB radiation in sunlight, causing DNA damage and subsequent tumorigenic mutations. These UVB-induced DNA damage products across the genome are repaired by the global genome NER (GG-NER) machinery. Functional GG-NER is essential for preventing mutations and skin tumorigenesis. One of the potential effective strategies for preventing skin cancer is enhancing GG-NER through dietary supplementation with a vitamin E derivative. However, its mechanism of action remains poorly understood. Recently, we discovered a novel role for vitamin E derivative in enhancing GG-NER. Guided by our preliminary data, we hypothesize that this dietary supplement enhances GG-NER and thus inhibits UVB- induced skin cancer. Our hypothesis will be tested in two Specific Aims. Aim 1 will determine the mechanism by which the vitamin E derivative regulates GG-NER. Aim 2 will determine the mechanism by which the vitamin E derivative affects UVB-induced skin tumorigenesis in mice. Successful completion of our proposed project will vastly expand our knowledge of the mechanism of action of the vitamin E derivative in GG-NER and skin cancer, and may provide new opportunities for developing better strategies to prevent and treat skin cancer using dietary supplement vitamin E derivative. Since GG-NER is critical for tumor suppression in the skin, lungs, and brain 18, our work here in GG-NER regulation by the vitamin E derivative may not only be significant for skin cancer, but may also be applicable to other tumor types as well.

摘要 建议补充的主要目标是确定膳食营养素的作用机制， 补充维生素E衍生物可以预防UVB诱导的皮肤癌， 父母补助金的范围。美国最常见的癌症皮肤癌的发病率持续上升 以惊人的速度。一个主要的风险因素是阳光中的UVB辐射，导致DNA损伤， 致瘤突变这些UVB诱导的DNA损伤产物在基因组中被修复， 全球基因组NER（GG-NER）机制。功能性GG-NER对于防止突变和皮肤 肿瘤发生提高GG-NER是预防皮肤癌的潜在有效策略之一 通过饮食补充维生素E衍生物。然而，其作用机制仍然很差 明白最近，我们发现了维生素E衍生物在增强GG-NER中的新作用。指导 根据我们的初步数据，我们假设这种膳食补充剂可以增强GG-NER，从而抑制UVB， 诱发皮肤癌。我们的假设将在两个具体目标中得到检验。目标1将决定机制 维生素E衍生物通过其调节GG-NER。目标2将确定维生素 E衍生物对UVB诱导的小鼠皮肤肿瘤发生的影响成功完成我们的项目 将极大地扩展我们对GG-NER和皮肤中维生素E衍生物作用机制的认识 癌症，并可能为开发更好的预防和治疗皮肤癌的策略提供新的机会 使用膳食补充剂维生素E衍生物。由于GG-NER对皮肤中的肿瘤抑制至关重要， 肺和大脑18，我们在维生素E衍生物调节GG-NER方面的工作不仅意义重大， 用于皮肤癌，但也可以适用于其他肿瘤类型。