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NOVA1 induction by inflammation and NOVA1 suppression by epigenetic regulation in head and neck squamous cell carcinoma

 Eun Kyung Kim  ;  Yoon Ah Cho  ;  Mi-kyoung Seo  ;  Hyunmi Ryu  ;  Byoung Chul Cho  ;  Yoon Woo Koh  ;  Sun Och Yoon 
 Scientific Reports, Vol.9(1) : 11231, 2019 
Journal Title
 Scientific Reports 
Issue Date
Neuro-oncological ventral antigen 1 (NOVA1) is known as a neuron-specific pre-mRNA binding splicing factor. Previously, it was shown to be highly upregulated in T lymphocytes, as well as fibroblasts/stromal spindle cells, in tertiary lymphoid tissues formed by the benign immune-inflammatory process, while it was frequently downregulated in tumor cells and other cells within the tumor microenvironment. Here, we sought to identify the mechanisms of NOVA1 modulation in head and neck squamous cell carcinoma (HNSCC). NOVA1 was induced by inflammatory-immune signals within the tumor microenvironment and was suppressed by epigenetic dysregulation, such as that with miR-146. We found attenuated expression of NOVA1 to be associated with non-oropharynx sites such as oral cavity, hypopharynx, and larynx, human papilloma virus (HPV)-negative SCC defined by immunohistochemistry for p16INK4a expression, fewer tumor infiltrating lymphocytes, and poor patient outcomes. Moreover, changes were discovered in epithelial mesenchymal transition-associated markers according to NOVA1 status. This study provides some insights to the underlying mechanism of NOVA1 regulation and suggests that NOVA1 may serve as a prognostic biomarker and potential therapeutic target for HNSCC in the future.
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1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Koh, Yoon Woo(고윤우)
Yoon, Sun Och(윤선옥) ORCID logo https://orcid.org/0000-0002-5115-1402
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
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