DataSheet_5_The DCMU Herbicide Shapes T-cell Functions By Modulating Micro-RNA Expression Profiles.pdf

DCMU [N-(3,4-dichlorophenyl)-N-dimethylurea] or diuron is a widely used herbicide, which can cause adverse effects on human, especially on immune cells, due to their intrinsic properties and wide distribution. These cells are important for fighting not only against virus or bacteria but also against neoplastic cell development. We developed an approach that combines functional studies and miRNA and RNA sequencing data to evaluate the effects of DCMU on the human immune response against cancer, particularly the one carried out by CD8+ T cells. We found that DCMU modulates the expression of miRNA in a dose-dependent manner, leading to a specific pattern of gene expression and consequently to a diminished cytokine and granzyme B secretions. Using mimics or anti-miRs, we identified several miRNA, such as hsa-miR-3135b and hsa-miR-21-5p, that regulate these secretions. All these changes reduce the CD8+ T cells’ cytotoxic activity directed against cancer cells, in vitro and in vivo in a zebrafish model. To conclude, our study suggests that DCMU reduces T-cell abilities, participating thus to the establishment of an environment conducive to cancer development.

DCMU（N-(3,4-二氯苯基)-N-二甲基脲）或称二氯笨脲，是一种广泛应用的除草剂，由于其固有性质和广泛分布，对人体尤其是免疫细胞产生不利影响。此类细胞对于抵抗病毒或细菌，以及抑制肿瘤细胞发展至关重要。本研究开发了一种结合功能研究和miRNA及RNA测序数据的方法，以评估DCMU对人类免疫系统对抗癌症的影响，特别是CD8+ T细胞执行的功能。研究发现，DCMU以剂量依赖性方式调节miRNA的表达，导致特定的基因表达模式，进而减少细胞因子和颗粒酶B的分泌。通过使用模拟物或反义miRNA，我们确定了如hsa-miR-3135b和hsa-miR-21-5p等miRNA，它们调节这些分泌过程。所有这些变化均降低了CD8+ T细胞对癌细胞体外及在斑马鱼模型中体内所执行的细胞毒活性。综上所述，本研究表明DCMU通过降低T细胞的效能，从而有助于营造有利于癌症发展的环境。