Department of Otolaryngology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Department of Otorhinolaryngology, The Third Hospital of Handan, Handan, Hebei 056001, P.R. China.
Mol Med Rep. 2021 Dec;24(6). doi: 10.3892/mmr.2021.12471. Epub 2021 Sep 30.
Forkhead box (FOX) proteins are multifaceted transcription factors that have been shown to be involved in cell cycle progression, proliferation and metastasis. FOXP4, a member of the FOX family, has been implicated in diverse biological processes in tumor initiation and progression. However, the molecular mechanisms of FOXP4 in laryngeal squamous cell carcinoma (LSCC) remain unknown. In the present study, differentially expressed transcripts in transforming growth factor‑β‑treated TU177 cells were screened using microarrays and it was found that FOXP4 was significantly upregulated. The high expression of FOXP4 was detected in LSCC tissues and cells, and predicted poor prognosis. The role of FOXP4 in laryngeal cancer cell proliferation, migration and invasion was determined by gain‑ and loss‑of‑function assays. Besides, FOXP4 was demonstrated to participate in the epithelial‑mesenchymal transition process at the mRNA and protein levels. Mechanically, FOXP4 directly bound to the promoter of lymphoid enhancer‑binding factor 1 and activated Wnt signaling pathway, which was confirmed via chromatin immunoprecipitation and luciferase reporter assays. Consequently, these findings provided novel mechanisms of FOXP4 in LSCC progression, which may be considered as potential therapeutic and prognostic targets for LSCC.
叉头框 (FOX) 蛋白是多功能转录因子,已被证明参与细胞周期进程、增殖和转移。FOXP4 是 FOX 家族的成员,与肿瘤发生和进展中的多种生物学过程有关。然而,FOXP4 在喉鳞状细胞癌 (LSCC) 中的分子机制尚不清楚。在本研究中,使用微阵列筛选转化生长因子-β处理的 TU177 细胞中的差异表达转录物,发现 FOXP4 显著上调。FOXP4 在 LSCC 组织和细胞中高表达,预测预后不良。通过增益和缺失功能测定确定了 FOXP4 在喉癌细胞增殖、迁移和侵袭中的作用。此外,FOXP4 在 mRNA 和蛋白质水平上被证明参与上皮-间充质转化过程。机制上,FOXP4 直接与淋巴增强结合因子 1 的启动子结合并激活 Wnt 信号通路,这通过染色质免疫沉淀和荧光素酶报告基因检测得到证实。因此,这些发现为 FOXP4 在 LSCC 进展中的作用提供了新的机制,可能被认为是 LSCC 的潜在治疗和预后靶点。