CXCL11 受 MED19 负调控，有利于乳腺癌抗肿瘤免疫浸润。
CXCL11 negatively regulated by MED19 favours antitumour immune infiltration in breast cancer.
机构信息
Oncology Institute, The Affiliated Hospital of Jiangnan University, Wuxi 214062, China.
Department of Breast Surgery, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214122, China.
出版信息
Cytokine. 2023 Feb;162:156106. doi: 10.1016/j.cyto.2022.156106. Epub 2022 Dec 10.
BACKGROUND
Through microarray results, we found that the C-X-C motif chemokine ligand 11 (CXCL11) was negatively regulated by mediator complex subunit 19 (MED19), a protumour factor. However, the biological role and potential mechanism of CXCL11 need to be explored in breast cancer (BRCA).
METHODS
The BRCA dataset was obtained from the Cancer Genome Atlas (TCGA) dataset. Our microarray data and the BRCA dataset of TCGA were analysed and visualized using the R software package. The mRNA and protein levels were measured by qRT-PCR and western blotting.
RESULTS
Inhibition of MED19 in MDA-MB-231 cells caused CXCL11 upregulation. The relative positive regulation of cytokine pathways was enriched after MED19 knockdown. High CXCL11 was determined to be positively correlated with immune response activation, increased antitumour immune cell infiltration, immune checkpoint molecule expression, and enhanced sensitivity to immunotherapy and chemotherapy. Collectively, CXCL11 promoted antitumour immunity and was regulated by MED19 in BRCA. Clarifying the prognostic value and underlying mechanism of CXCL11 in BRCA could provide a theoretical basis to find new diagnostic and therapeutic targets.
背景
通过微阵列结果，我们发现 C-X-C 基序趋化因子配体 11（CXCL11）受到肿瘤促进因子中介体复合物亚基 19（MED19）的负调控。然而，CXCL11 在乳腺癌（BRCA）中的生物学作用和潜在机制仍需探索。
方法
从癌症基因组图谱（TCGA）数据库中获取 BRCA 数据集。我们使用 R 软件包对微阵列数据和 TCGA 的 BRCA 数据集进行分析和可视化。通过 qRT-PCR 和 Western blot 测量 mRNA 和蛋白质水平。
结果
在 MDA-MB-231 细胞中抑制 MED19 会导致 CXCL11 的上调。MED19 敲低后，细胞因子途径的相对正调控被富集。高表达的 CXCL11 与免疫反应激活、增加抗肿瘤免疫细胞浸润、免疫检查点分子表达以及增强对免疫治疗和化疗的敏感性呈正相关。总的来说，CXCL11 在 BRCA 中促进抗肿瘤免疫，并受 MED19 调节。阐明 CXCL11 在 BRCA 中的预后价值和潜在机制，可以为寻找新的诊断和治疗靶点提供理论依据。
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