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Review
. 2024 May 3;22(1):418.
doi: 10.1186/s12967-024-05169-9.

Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets

Mengchen Xu #  1 , Yiming Hou #  1 , Na Li  2   3 , Wenqian Yu  4 , Lei Chen  5
Affiliations
Review

Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets

Mengchen Xu et al. J Transl Med. .

Abstract

The onerous health and economic burden associated with head and neck squamous cell carcinoma (HNSCC) is a global predicament. Despite the advent of novel surgical techniques and therapeutic protocols, there is an incessant need for efficacious diagnostic and therapeutic targets to monitor the invasion, metastasis and recurrence of HNSCC due to its substantial morbidity and mortality. The differential expression patterns of histone deacetylases (HDACs), a group of enzymes responsible for modifying histones and regulating gene expression, have been demonstrated in neoplastic tissues. However, there is limited knowledge regarding the role of HDACs in HNSCC. Consequently, this review aims to summarize the existing research findings and explore the potential association between HDACs and HNSCC, offering fresh perspectives on therapeutic approaches targeting HDACs that could potentially enhance the efficacy of HNSCC treatment. Additionally, the Cancer Genome Atlas (TCGA) dataset, CPTAC, HPA, OmicShare, GeneMANIA and STRING databases are utilized to provide supplementary evidence on the differential expression of HDACs, their prognostic significance and predicting functions in HNSCC patients.

Keywords: Epigenetic therapy; Head and neck squamous cell carcinoma; Histone deacetylases; Mechanism.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Fig. 1
Fig. 1
The global prevalence and distribution of HNSCC. The global prevalence of HNSCC is depicted through the estimated age-standardized rate for both genders. The data utilized is sourced from GLOBOCAN, 2022. The map was generated employing online mapping tool (https://gco.iarc.fr/today/online-analysis-map). The selected cancer sites encompass hypopharynx, larynx, lip, oral cavity, nasopharynx, salivary glands and oropharynx
Fig. 2
Fig. 2
HDACs mediated-histone modifications affect key biological processes in HNSCC cell proliferation, angiogenesis, apoptosis and metastasis. Created with Figdraw (www.figdraw.com)
Fig. 3
Fig. 3
Relative mRNA and protein expression comparisons of different HDAC family in tumor and normal tissues. The two-tailed unpaired t-test was employed to evaluate the relative mRNA expression levels of different HDAC family members using TCGA database, which includes RNA sequencing data from 520 HNSCC samples and 44 normal samples. The protein levels of different HDACs were analyzed through CPTAC database, encompassing 108 HNSCC samples and 71 normal samples, with validation by HPA database. The Kaplan–Meier plotter highlighted the prognostic importance of HDAC mRNA expressions in HNSCC patients. Data represent the mean ± SD. *p < 0.05
Fig. 4
Fig. 4
The predictive functions and pathways of HDACs along with their neighboring genes in HNSCC. A Network of HDACs and their neighboring genes was constructed using GeneMANIA (http://genemania.org). B HDAC family protein–protein interaction (PPI) network by STRING (https://string-db.org). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of HDAC genes was shown in C (https://www.omicshare.com). Gene ontology (GO) enrichment analysis of HDAC genes was conducted based on molecular function (D), cellular component (E) and biological process (F) (https://www.omicshare.com)
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