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

Research output: Contribution to journalArticle

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
Number of pages1
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Aug 2

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Epigenomics
Inflammation
Antigens
Tumor Microenvironment
Papillomaviridae
Tumor-Infiltrating Lymphocytes
Hypopharynx
Epithelial-Mesenchymal Transition
RNA Precursors
Lymphoid Tissue
Stromal Cells
Larynx
Carcinoma, squamous cell of head and neck
Mouth
Down-Regulation
Fibroblasts
Biomarkers
Immunohistochemistry
T-Lymphocytes
Neurons

All Science Journal Classification (ASJC) codes

  • General

Cite this

@article{e1f32cece184453d8a602ffebd41566a,
title = "NOVA1 induction by inflammation and NOVA1 suppression by epigenetic regulation in head and neck squamous cell carcinoma",
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.",
author = "Kim, {Eun Kyung} and Cho, {Yoon Ah} and Seo, {Mi Kyoung} and Hyunmi Ryu and Cho, {Byoung Chul} and Koh, {Yoon Woo} and Yoon, {Sun Och}",
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NOVA1 induction by inflammation and NOVA1 suppression by epigenetic regulation in head and neck squamous cell carcinoma. / Kim, Eun Kyung; Cho, Yoon Ah; Seo, Mi Kyoung; Ryu, Hyunmi; Cho, Byoung Chul; Koh, Yoon Woo; Yoon, Sun Och.

In: Scientific reports, Vol. 9, No. 1, 02.08.2019.

Research output: Contribution to journalArticle

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