Preprint Article Version 1 This version is not peer-reviewed

Aberrant Epigenetic Regulation in Head and Neck Cancer Due to Distinct EZH2 Overexpression and DNA Hypermethylation

Version 1 : Received: 24 October 2018 / Approved: 24 October 2018 / Online: 24 October 2018 (10:34:10 CEST)

A peer-reviewed article of this Preprint also exists.

Mochizuki, D.; Misawa, Y.; Kawasaki, H.; Imai, A.; Endo, S.; Mima, M.; Yamada, S.; Nakagawa, T.; Kanazawa, T.; Misawa, K. Aberrant Epigenetic Regulation in Head and Neck Cancer Due to Distinct EZH2 Overexpression and DNA Hypermethylation. Int. J. Mol. Sci. 2018, 19, 3707. Mochizuki, D.; Misawa, Y.; Kawasaki, H.; Imai, A.; Endo, S.; Mima, M.; Yamada, S.; Nakagawa, T.; Kanazawa, T.; Misawa, K. Aberrant Epigenetic Regulation in Head and Neck Cancer Due to Distinct EZH2 Overexpression and DNA Hypermethylation. Int. J. Mol. Sci. 2018, 19, 3707.

Journal reference: Int. J. Mol. Sci. 2018, 19, 3707
DOI: 10.3390/ijms19123707

Abstract

EZH2 overexpression is associated with tumor proliferation, metastasis, and poor prognosis. Targeting and inhibiting EZH2 may be an effective therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). We previously analyzed EZH2 mRNA expression in a well-characterized dataset of 230 (110 original and 120 validation cohorts) human head and neck cancer samples. This study aimed to investigate the effects of inhibiting EZH2, either via RNA interference or via pharmacotherapy, on HNSCC growth. EZH2 upregulation was significantly correlated with recurrence (P < 0.001) and the methylation index of tumor suppressor genes (P < 0.05). DNMT3A was significantly upregulated upon EZH2 upregulation (P = 0.043). Univariate analysis revealed that EZH2 upregulation was associated with poor disease-free survival (log-rank test, P < 0.001). In multivariate analysis, EZH2 upregulation was evaluated as a significant independent prognostic factor of disease-free survival (hazard ratio: 2.085, 95% confidence interval: 1.390–3.127; P < 0.001). Cells treated with RNA interference and DZNep, an EZH2 inhibitor, showed the most dramatic changes in expression, accompanied with a reduction in the growth and survival of FaDu cells. These findings suggest that EZH2 upregulation is correlated with tumor aggressiveness and adverse patient outcomes in HNSCC. Evaluation of EZH2 expression might help predict the prognosis of HNSCC patients.

Subject Areas

EZH2; epigenetic regulation; DZNep; tumor-related genes; head and neck cancer

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.