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Valproic acid exposure alters histone deacetylase mRNA expression profile in oral cancer and premalignant cell lines

  • Authors:
    • Ahmed S.K. Al‑Khafaji
    • Yasir B. Qaddoori
    • Haidar H. Alabdei
    • Lydia M. Wang
  • View Affiliations / Copyright

    Affiliations: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L7 8TX, UK, Department of Biology, College of Science, University of Baghdad, Baghdad 10071, Iraq, Scientific Department, Warith International Cancer Institute, Karbala 56001, Iraq, Centre for Haemato‑Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK
    Copyright: © Al‑Khafaji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 135
    |
    Published online on: June 11, 2025
       https://doi.org/10.3892/br.2025.2013
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Abstract

The common frequent precursors to head and neck squamous cell carcinoma (HNSCC) are oral dysplasias (ODs). Nonetheless, methods for prediction or prevention of the malignant transformation of OD are unreliable. Therefore, oral HNSCC is often diagnosed in the advanced stages of the disease. Abnormalities in histone acetylation in oral cancers include aberrant histone deacetylase (HDAC) expression. Therefore, HDAC inhibitors (HDACis) have potential in the treatment of HNSCC and chemoprevention for patients with high‑risk OD. Valproic acid (VPA), is an anti‑epileptic drug that shows HDACi activity, specifically targeting Class IIa HDACs, with efficacy against HNSCC cells; however, the molecular changes in response to VPA remain unclear. The present study aimed to determine how VPA exposure affects Class IIa HDAC mRNA expression in oral cancer cell lines (UM‑SCC‑10A, UM‑SCC‑11B, UM‑SCC‑12, UM‑SCC‑17A, HN5, PE/CA‑PJ15, UM‑SCC‑1, BHY, PE/CA‑PJ41 and UM‑SCC‑81B) and premalignant cells (D19, D20 and D35). Reverse transcription‑quantitative PCR (RT‑qPCR) revealed a trend of upregulation of HDAC4 and HDAC5, and downregulation of HDAC7 in all of the examined cells in response to 1 mM VPA exposure at different time points (6, 24 or 48 h). A total of three cell lines (precancerous D20 tongue immortal dysplastic cells, BHY oral squamous cell carcinoma cells and UM‑SCC‑10A laryngeal squamous cell carcinoma cells; ≥2‑fold differences in HDAC expression following VPA treatment) were selected for further investigations using RT‑qPCR to confirm the VPA‑mediated alteration of HDAC mRNA expression. VPA‑dependent epigenetic reprogramming resulted in transcriptional alterations of Class IIa HDACs in HNSCC and premalignant cells. The clinical relevance of these alterations in the pathogenesis of HNSCC must be further determined.
View Figures

Figure 1

mRNA expression levels of Class IIa
HDACs in oral cancerous and premalignant cell lines following VPA
exposure were compared with untreated counterpart cells at three
different time points (6, 24 and 48 h). The P-values of significant
differences between the examined groups (HDAC expression in
VPA-treated cells compared with untreated controls) were indicated
as *P<0.05, **P<0.01 and
***P<0.005. HDAC, histone deacetylase; V, expression
in VPA-treated cells; VPA, valproic acid; C, control untreated
cells; RQ, relative quantity of mRNA expression; NS, not
significant.

Figure 2

Effects of valproic acid treatment on
Class IIa HDACs mRNA expression in BHY cell line.
***P<0.005. HDAC, histone deacetylase; RQ, relative
quantity of mRNA expression; NS, not significant.

Figure 3

Effects of valproic acid treatment on
Class IIa HDACs mRNA expression in UM-SCC-10A cell line.
*P<0.05, **P<0.01,
***P<0.005. HDAC, histone deacetylase; RQ, relative
quantity of mRNA expression; NS, not significant.

Figure 4

Effects of valproic acid treatment on
Class IIa HDACs mRNA expression in D20 cell line.
*P<0.05, **P<0.01,
***P<0.005. HDAC, histone deacetylase; RQ, relative
quantity of mRNA expression; NS, not significant.
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Copy and paste a formatted citation
Spandidos Publications style
Al‑Khafaji AS, Qaddoori YB, Alabdei HH and Wang LM: Valproic acid exposure alters histone deacetylase mRNA expression profile in oral cancer and premalignant cell lines. Biomed Rep 23: 135, 2025.
APA
Al‑Khafaji, A.S., Qaddoori, Y.B., Alabdei, H.H., & Wang, L.M. (2025). Valproic acid exposure alters histone deacetylase mRNA expression profile in oral cancer and premalignant cell lines. Biomedical Reports, 23, 135. https://doi.org/10.3892/br.2025.2013
MLA
Al‑Khafaji, A. S., Qaddoori, Y. B., Alabdei, H. H., Wang, L. M."Valproic acid exposure alters histone deacetylase mRNA expression profile in oral cancer and premalignant cell lines". Biomedical Reports 23.2 (2025): 135.
Chicago
Al‑Khafaji, A. S., Qaddoori, Y. B., Alabdei, H. H., Wang, L. M."Valproic acid exposure alters histone deacetylase mRNA expression profile in oral cancer and premalignant cell lines". Biomedical Reports 23, no. 2 (2025): 135. https://doi.org/10.3892/br.2025.2013
Copy and paste a formatted citation
x
Spandidos Publications style
Al‑Khafaji AS, Qaddoori YB, Alabdei HH and Wang LM: Valproic acid exposure alters histone deacetylase mRNA expression profile in oral cancer and premalignant cell lines. Biomed Rep 23: 135, 2025.
APA
Al‑Khafaji, A.S., Qaddoori, Y.B., Alabdei, H.H., & Wang, L.M. (2025). Valproic acid exposure alters histone deacetylase mRNA expression profile in oral cancer and premalignant cell lines. Biomedical Reports, 23, 135. https://doi.org/10.3892/br.2025.2013
MLA
Al‑Khafaji, A. S., Qaddoori, Y. B., Alabdei, H. H., Wang, L. M."Valproic acid exposure alters histone deacetylase mRNA expression profile in oral cancer and premalignant cell lines". Biomedical Reports 23.2 (2025): 135.
Chicago
Al‑Khafaji, A. S., Qaddoori, Y. B., Alabdei, H. H., Wang, L. M."Valproic acid exposure alters histone deacetylase mRNA expression profile in oral cancer and premalignant cell lines". Biomedical Reports 23, no. 2 (2025): 135. https://doi.org/10.3892/br.2025.2013
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