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

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Abstract

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.

Original languageEnglish
Article number11231
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT) (No. NRF-2019R1A2C1002370). We would like to thank Dong-Su Jang, MFA (Medical Illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Korea) for his help with the illustrations.

Publisher Copyright:
© 2019, The Author(s).

All Science Journal Classification (ASJC) codes

  • General

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