Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Int J Oncol. 2017 Oct;51(4):1045-1054. doi: 10.3892/ijo.2017.4094. Epub 2017 Aug 9.
Forkhead box M1 (FoxM1), a member of the Fox family of transcriptional factors, is involved in the development of various human malignancies. However, the expression level of FoxM1 and its functional role in hypopharyngeal squamous cell carcinoma (HSCC) remained unclear to date. The aim of the present study was to investigate the FoxM1 expression in 63 HSCC and 20 adjacent normal tissues, as well as to evaluate its association with the clinicopathological parameters and its diagnostic value in HSCC. To further explore the biological function of FoxM1 in vitro, siRNAs were used to knockdown the expression of FoxM1 in the HSCC cell line Fadu. The results revealed that FoxM1 protein was highly expressed in HSCC tissues and that its high expression was closely associated with HSCC tumor differentiation (P=0.004), tumor size (P=0.002), clinical stage (P=0.001), lymph node metastasis (P=0.002), treatment (P=0.045) and expression of the proliferation marker Ki-67 (P<0.001). Additionally, the elevated expression of FoxM1 in HSCC patients consistently predicted a poor survival time. Knockdown of FoxM1 expression blocked Fadu cell proliferation and promoted apoptosis, and also led to the downregulation of cyclin A1 expression. Furthermore, decreased expression of FoxM1 markedly impeded cell migration and reversed the epithelial-mesenchymal transition phenotype, as indicated by decreased expression of vimentin and increased expression of E-cadherin in Fadu cells. These results indicate that FoxM1 may act as an oncogene and serve as a therapeutic target against malignant progression in HSCC.
叉头框转录因子 M1（FoxM1）是 Fox 家族转录因子的一员，参与多种人类恶性肿瘤的发生。然而，FoxM1 的表达水平及其在下咽鳞癌（HSCC）中的功能作用至今仍不清楚。本研究旨在检测 63 例 HSCC 组织和 20 例癌旁正常组织中 FoxM1 的表达水平，并评估其与临床病理参数的相关性及其对 HSCC 的诊断价值。为了进一步探讨 FoxM1 在体外的生物学功能，我们使用 siRNA 敲低 HSCC 细胞系 Fadu 中 FoxM1 的表达。结果显示，FoxM1 蛋白在上皮组织中高表达，且其高表达与 HSCC 肿瘤分化（P=0.004）、肿瘤大小（P=0.002）、临床分期（P=0.001）、淋巴结转移（P=0.002）、治疗方法（P=0.045）和增殖标志物 Ki-67 的表达（P<0.001）密切相关。此外，FoxM1 在 HSCC 患者中的高表达一致预示着较差的生存时间。敲低 FoxM1 的表达可抑制 Fadu 细胞增殖并促进细胞凋亡，同时下调 cyclin A1 的表达。此外，下调 FoxM1 的表达可显著抑制细胞迁移并逆转上皮间质转化表型，Fadu 细胞中波形蛋白的表达下调和 E-钙黏蛋白的表达上调均提示了这一点。这些结果表明，FoxM1 可能作为一种癌基因，成为针对 HSCC 恶性进展的治疗靶点。
