Objective. Forkhead box O 4 (FOXO4), a key albumen in the forkhead box O (FOXOs) family, plays crucial roles as a tumor suppressor in the cancer development. In our previous study, Peroxiredoxin1 (Prx1) promoted the development of oral cancer and was predicted to bind to FOXO4. The aim of this study was to investigate the clinicopathological significance of FOXO4 expression and its potential mechanism in head and neck squamous cell carcinomas (HNSCC). Methods. The function of FOXO4 correlation with HNSCC prognosis was analyzed via ONCOMINE, UALCAN, Human Protein Atlas, and cBioPortal. The expression of FOXO4 was detected in Prx1 silenced CaL27 and SCC9 cell lines by Western blot. FOXO4 protein expression was observed via immunohistochemistry (IHC) and the binding of Prx1 to FOXO4 measured by Duolink analysis in a 4-nitro-quinoline-1-oxide- (4NQO-) induced tongue carcinogenesis model in Prx1^+/+ and Prx1^+/− mice. Results. By the analysis of Bioinformation Databases, there was a significant interaction of FOXO4 down expression to clinical tumor stages and pathological grades in the patients with HNSCC. Reduced mRNA and protein expression of FOXO4 were found to be significantly correlated with the poor overall survival (OS) of HNSCC patients. FOXO4 expression is negatively related to Prx1 significantly in HNSCC tissues. By employing a 4NQO-induced oral carcinogenesis mouse model, we confirmed that FOXO4 expression was reduced in 4NQO-induced squamous cell carcinoma (SCC) tongue tissues compared with those in normal tissues. Prx1 knockdown resulted in the upregulation of FOXO4 expression in the SCC tissues and CaL27 and SCC9 cell lines. Furthermore, the interaction of Prx1 with FOXO4 was observed in mouse tongue tissues by Duolink analysis. Conclusion. FOXO4 plays an important role in the development of HNSCC. The lower expression of FOXO4 is significantly correlated with the shorter OS in patients with HNSCC. FOXO4 is negatively regulated via interaction with Prx1. FOXO4 could be a potential molecular target for the treatment and prognosis of HNSCC.

中文翻译：

---

FOXO4在头颈部鳞状细胞癌中的表达及其与Prx1的相关性的临床病理学意义

客观。Forkhead box O 4 (FOXO4) 是 Forkhead box O (FOXOs) 家族中的关键蛋白，在癌症发展中作为肿瘤抑制因子发挥着至关重要的作用。在我们之前的研究中，Peroxiredoxin1 (Prx1) 促进了口腔癌的发展，并预计与 FOXO4 结合。本研究的目的是探讨 FOXO4 表达的临床病理学意义及其在头颈部鳞状细胞癌 (HNSCC) 中的潜在机制。方法. 通过 ONCOMINE、UALCAN、Human Protein Atlas 和 cBioPortal 分析 FOXO4 与 HNSCC 预后的相关性。通过Western印迹法在Prx1沉默的CaL27和SCC9细胞系中检测到FOXO4的表达。^{在 Prx1 +/+}和 Prx1 ^+/的 4-硝基-喹啉-1-氧化物- (4NQO-) 诱导的舌癌发生模型中，通过免疫组织化学 (IHC) 观察 FOXO4 蛋白表达，并通过 Duolink 分析测量 Prx1 与 FOXO4 的结合。^-老鼠。结果. 通过对生物信息数据库的分析，FOXO4的下调与HNSCC患者的临床肿瘤分期和病理分级存在显着的交互作用。研究发现 FOXO4 的 mRNA 和蛋白表达降低与 HNSCC 患者较差的总生存期 (OS) 显着相关。FOXO4 表达与 HNSCC 组织中的 Prx1 显着负相关。通过采用 4NQO 诱导的口腔癌发生小鼠模型，我们证实与正常组织相比，4NQO 诱导的鳞状细胞癌 (SCC) 舌组织中 FOXO4 的表达降低。Prx1 敲低导致 SCC 组织和 CaL27 和 SCC9 细胞系中 FOXO4 表达的上调。此外，通过 Duolink 分析在小鼠舌组织中观察到 Prx1 与 FOXO4 的相互作用。结论。FOXO4 在 HNSCC 的发生发展中起重要作用。FOXO4 的低表达与 HNSCC 患者的较短 OS 显着相关。FOXO4 通过与 Prx1 的相互作用受到负调控。FOXO4 可能是 HNSCC 治疗和预后的潜在分子靶点。