AIRE 在口腔鳞状细胞癌中被诱导，并促进癌基因表达。
AIRE is induced in oral squamous cell carcinoma and promotes cancer gene expression.
机构信息
Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
出版信息
PLoS One. 2020 Feb 3;15(2):e0222689. doi: 10.1371/journal.pone.0222689. eCollection 2020.
Autoimmune regulator (AIRE) is a transcriptional regulator that is primarily expressed in medullary epithelial cells, where it induces tissue-specific antigen expression. Under pathological conditions, AIRE expression is induced in epidermal cells and promotes skin tumor development. This study aimed to clarify the role of AIRE in the pathogenesis of oral squamous cell carcinoma (OSCC). AIRE expression was evaluated in six OSCC cell lines and in OSCC tissue specimens. Expression of STAT1, ICAM1, CXCL10, CXCL11, and MMP9 was elevated in 293A cells stably expressing AIRE, and conversely, was decreased in AIRE-knockout HSC3 OSCC cells when compared to the respective controls. Upregulation of STAT1, and ICAM in OSCC cells was confirmed in tissue specimens by immunohistochemistry. We provide evidence that AIRE exerts transcriptional control in cooperation with ETS1. Expression of STAT1, ICAM1, CXCL10, CXCL11, and MMP9 was increased in 293A cells upon Ets1 transfection, and coexpression of AIRE further increased the expression of these proteins. AIRE coprecipitated with ETS1 in a modified immunoprecipitation assay using formaldehyde crosslinking. Chromatin immunoprecipitation and quantitative PCR analysis revealed that promoter fragments of STAT1, ICAM1, CXCL10, and MMP9 were enriched in the AIRE precipitates. These results indicate that AIRE is induced in OSCC and supports cancer-related gene expression in cooperation with ETS1. This is a novel function of AIRE in extrathymic tissues under the pathological condition.
自身免疫调节因子（AIRE）是一种主要在髓质上皮细胞中表达的转录调节因子，它诱导组织特异性抗原表达。在病理条件下，AIRE 在表皮细胞中被诱导，并促进皮肤肿瘤的发展。本研究旨在阐明 AIRE 在口腔鳞状细胞癌（OSCC）发病机制中的作用。评估了 AIRE 在六种 OSCC 细胞系和 OSCC 组织标本中的表达。在稳定表达 AIRE 的 293A 细胞中，STAT1、ICAM1、CXCL10、CXCL11 和 MMP9 的表达升高，而在 AIRE 敲除的 HSC3 OSCC 细胞中，与各自的对照相比，其表达降低。通过免疫组织化学证实了 STAT1 和 ICAM 在 OSCC 细胞中的组织标本中的上调。我们提供的证据表明，AIRE 与 ETS1 合作发挥转录控制作用。在 Ets1 转染的 293A 细胞中，STAT1、ICAM1、CXCL10、CXCL11 和 MMP9 的表达增加，而 AIRE 的共表达进一步增加了这些蛋白的表达。在使用甲醛交联的改良免疫沉淀测定中，AIRE 与 ETS1 共沉淀。染色质免疫沉淀和定量 PCR 分析显示，STAT1、ICAM1、CXCL10 和 MMP9 的启动子片段在 AIRE 沉淀中富集。这些结果表明，AIRE 在 OSCC 中被诱导，并与 ETS1 合作支持与癌症相关的基因表达。这是 AIRE 在病理条件下在胸腺外组织中的新功能。
Zotero 插件