Al-Khafaji Ahmed S K, Qaddoori Yasir B, Alabdei Haidar H, Wang Lydia M
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.
Biomed Rep. 2025 Jun 11;23(2):135. doi: 10.3892/br.2025.2013. eCollection 2025 Aug.
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.
头颈部鳞状细胞癌（HNSCC）常见的前期病变是口腔发育异常（OD）。然而，预测或预防OD恶变的方法并不可靠。因此，口腔HNSCC常常在疾病晚期才被诊断出来。口腔癌中组蛋白乙酰化异常包括组蛋白去乙酰化酶（HDAC）表达异常。因此，HDAC抑制剂（HDACi）在HNSCC治疗及高危OD患者的化学预防方面具有潜力。丙戊酸（VPA）是一种抗癫痫药物，具有HDACi活性，特异性靶向IIa类HDACs，对HNSCC细胞有效；然而，VPA作用后的分子变化仍不清楚。本研究旨在确定VPA处理如何影响口腔癌细胞系（UM-SCC-10A、UM-SCC-11B、UM-SCC-12、UM-SCC-17A、HN5、PE/CA-PJ15、UM-SCC-1、BHY、PE/CA-PJ41和UM-SCC-81B）及癌前细胞（D19、D20和D35）中IIa类HDAC mRNA的表达。逆转录定量PCR（RT-qPCR）显示，在不同时间点（6、24或48小时）暴露于1 mM VPA后，所有检测细胞中HDAC4和HDAC5呈上调趋势，HDAC7呈下调趋势。总共选择了三个细胞系（癌前D20舌永生化发育异常细胞、BHY口腔鳞状细胞癌细胞和UM-SCC-10A喉鳞状细胞癌细胞；VPA处理后HDAC表达差异≥2倍），使用RT-qPCR进一步研究以确认VPA介导的HDAC mRNA表达改变。VPA依赖的表观遗传重编程导致HNSCC及癌前细胞中IIa类HDACs的转录改变。这些改变在HNSCC发病机制中的临床相关性必须进一步确定。
