The resistance of oral squamous cell carcinoma (OSCC) cells to cisplatin remains a tough nut to crack in OSCC therapy. Homeobox A1 (HOXA1) overexpression has been detected in head and neck squamous carcinoma (HNSC). Accordingly, this study aims to explore the potential role and mechanism of HOXA1 on cisplatin resistance in OSCC. The expression of HOXA1 in HNSC and its role in overall survival (OS) rate of OSCC patients were analyzed by bioinformatic analysis. Following transfection as needed, OSCC cells were induced by different concentrations of cisplatin, and the cell viability and apoptosis were evaluated by cell counting kit-8 and flow cytometry assays. The mRNA and protein expression levels of HOXA1 and the phosphorylation of IκBα and p65 were determined by real-time quantitative PCR and western blot. HOXA1 expression level was upregulated in HNSC tissues and OSCC cells. Overexpressed HOXA1 was correlated with a low OS rate of OSCC patients. Cisplatin exerted an anti-cancer effect on OSCC cells. HOXA1 silencing or cisplatin suppressed OSCC cell viability, boosted the apoptosis, and repressed the phosphorylation of IκBα and p65. Intriguingly, the combination of HOXA1 silencing and cisplatin generated a stronger anti-cancer effect on OSCC cells than their single use. HOXA1 silencing attenuates cisplatin resistance of OSCC cells via IκB/NF-κB signaling pathway, hinting that HOXA1 is a biomarker associated with OSCC and HOXA1 silencing can enhance the sensitivity of OSCC cells to cisplatin.

中文翻译：

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HOXA1沉默通过IκB/NF-κB信号通路抑制口腔鳞状细胞癌细胞的顺铂耐药。

口腔鳞状细胞癌（OSCC）细胞对顺铂的耐药性仍然是口腔鳞状细胞癌治疗中的一个难题。在头颈鳞状细胞癌 (HNSC) 中检测到同源框 A1 (HOXA1) 过度表达。因此，本研究旨在探讨HOXA1在OSCC顺铂耐药中的潜在作用和机制。通过生物信息学分析HOXA1在HNSC中的表达及其对OSCC患者总生存率的影响。根据需要转染后，用不同浓度的顺铂诱导OSCC细胞，并通过细胞计数kit-8和流式细胞仪检测细胞活力和凋亡。通过实时定量PCR和蛋白质印迹法测定HOXA1的mRNA和蛋白表达水平以及IκBα和p65的磷酸化。HNSC 组织和 OSCC 细胞中 HOXA1 表达水平上调。HOXA1 过度表达与 OSCC 患者的低 OS 率相关。顺铂对 OSCC 细胞具有抗癌作用。HOXA1 沉默或顺铂抑制 OSCC 细胞活力，促进细胞凋亡，并抑制 IκBα 和 p65 的磷酸化。有趣的是，HOXA1沉默和顺铂的组合对OSCC细胞产生比单独使用更强的抗癌作用。HOXA1沉默通过IκB/NF-κB信号通路减弱OSCC细胞的顺铂耐药性，提示HOXA1是与OSCC相关的生物标志物，HOXA1沉默可以增强OSCC细胞对顺铂的敏感性。