AIRE is induced in oral squamous cell carcinoma and promotes cancer gene expression

Chi Thi Kim Nguyen, Wanlada Sawangarun, Masita Mandasari, Kei ichi Morita, Hiroyuki Harada, Kou Kayamori, Akira Yamaguchi, Kei Sakamoto

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Abstract

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.

Original languageEnglish
Article numbere0222689
JournalPloS one
Volume15
Issue number2
DOIs
Publication statusPublished - 1 Jan 2020

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Nguyen, C. T. K., Sawangarun, W., Mandasari, M., Morita, K. I., Harada, H., Kayamori, K., ... Sakamoto, K. (2020). AIRE is induced in oral squamous cell carcinoma and promotes cancer gene expression. PloS one, 15(2), [e0222689]. https://doi.org/10.1371/journal.pone.0222689