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

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.

A systematic and comprehensive analysis of colorectal squamous cell carcinoma: Implication for diagnosis and treatment

“…34,35 Overexpression of STAT1 was observed in many SCCs and can promote the malignant ability of SCC. [36][37][38] Our findings suggested that TP63 and STAT1 may play a critical role in CSCC, and more studies on their mechanisms are necessary for the future.…”

Does a common genetic event exist for familial thyroid cancer? Results from a large family with FNMTC

“…AIRE, the autoimmune regulator, plays a key role in shaping central immunological tolerance by facilitating the negative selection of T cells. AIRE has been associated with the polyglandular syndrome type 1 (APS1) [40] and with cancer [41][42][43]. According with the literature [44] and with PROMO, a virtual laboratory for the identi cation of putative transcription factor binding sites, ERK1/2, which is linked to PRKC , activates Ets and Elk1 potential TF for AIRE.…”

Exploring genetic and immune underpinnings of the sexual dimorphism in tumor response to immune checkpoints inhibitors: A narrative review

“…AIRE is a transcription factor expressed by thymic ( Anderson et al., 2002 ) and extrathymic ( Poliani et al., 2010 ) cells, including stromal ( Bergström et al., 2019 ) and circulating ( Suzuki et al., 2008 ) elements, displaying features shared with dendritic cells (DCs) and therefore critically implicated in central tolerance. Intriguingly, animal models ( Zhu et al., 2013 ) and human studies ( Nguyen et al., 2020 ; Kalra et al., 2018 ) have pointed to a regulatory role of AIRE in cancer immune surveillance. However, this contention cannot be widely applied to a variety of neoplastic diseases since conflicting results have been reported ( Klamp et al., 2006 ).…”