Luo Shaohao, Bai Yunfei, Wang Boqian, Xu Haixia, Zhang Shu, Guo Gang, Li Xin, Sun Hongyang, Cui Xiaobo
Graduate School, Inner Mongolia Medical University.
Department of Otolaryngology, Head and Neck Surgery, the Affiliated Hospital of Inner Mongolia Medical University.
Tohoku J Exp Med. 2025 Mar 27;265(3):161-171. doi: 10.1620/tjem.2024.J073. Epub 2024 Aug 1.
Homeobox A1 (HOXA1) is implicated in the progression of various cancers, but its biological function in laryngeal cancer (LC) remains undefined, which is the foothold of our study. Bioinformatics analysis and survival analysis were performed to predict HOXA1 expression in LC tissues, and the prognostic relationship between high HOXA1 expression and LC. Whether high HOXA1 expression correlated with the clinical characteristics and prognosis of LC patients was analyzed. LC cell viability and sensitivity to cisplatin were determined by Methyl thiazolyl tetrazolium assay. The cell migration, invasion, and cell cycle after transfection were examined by Wound healing, Transwell, and flow cytometry assays, respectively. The corresponding mRNA and protein expressions were measured by quantitative real-time PCR or Western blot. A higher expression of HOXA1 was detected in LC tissues, which was found to be relevant to poor prognosis of LC patients. The association of high expression of HOXA1 with lymph node and clinical stage was also confirmed. Silencing of HOXA1 in LC cells enhanced the cell sensitivity to cisplatin, inhibited viability, migration, invasion and cell cycle, and reduced N-Cadherin, Vimentin, PCNA, p-AKT and p-mTOR expressions, while overexpression of HOXA1 had the opposite effects. Collectively, HOXA1 boosts migration, invasion and cell cycle, while suppressing cisplatin sensitivity of LC cells by mediating AKT/mTOR pathway, hinting that HOXA1 is a promising biomarker for diagnosis and prognosis of LC in clinical practice.
同源框A1（HOXA1）与多种癌症的进展有关，但其在喉癌（LC）中的生物学功能仍不明确，这是我们研究的立足点。进行生物信息学分析和生存分析以预测HOXA1在LC组织中的表达，以及高HOXA1表达与LC之间的预后关系。分析了高HOXA1表达是否与LC患者的临床特征和预后相关。通过甲基噻唑基四氮唑法测定LC细胞活力和顺铂敏感性。分别通过伤口愈合、Transwell和流式细胞术检测转染后的细胞迁移、侵袭和细胞周期。通过定量实时PCR或蛋白质印迹法测量相应的mRNA和蛋白质表达。在LC组织中检测到较高的HOXA1表达，发现其与LC患者的不良预后相关。还证实了HOXA1高表达与淋巴结及临床分期的关联。沉默LC细胞中的HOXA1可增强细胞对顺铂的敏感性，抑制活力、迁移、侵袭和细胞周期，并降低N-钙黏蛋白、波形蛋白、增殖细胞核抗原、磷酸化AKT和磷酸化mTOR的表达，而HOXA1的过表达则产生相反的效果。总体而言，HOXA1通过介导AKT/mTOR途径促进LC细胞的迁移、侵袭和细胞周期，同时抑制其对顺铂的敏感性，这表明HOXA1在临床实践中是一种有前景的LC诊断和预后生物标志物。
