Department of Oral Medicine, Qilu Hospital, Institute of Stomatology, Shandong University, Jinan, Shandong, China.
Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8306-8314. doi: 10.26355/eurrev_201812_16528.
Growing evidence indicated that long noncoding RNAs (lncRNAs) played important roles in tumor initiation and progression. In this study, we aimed to investigate the expression pattern, clinical significance, and biological function of lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) in oral squamous cell carcinoma (OSCC).
We evaluated the expression levels of FTH1P3 in OSCC tissues, adjacent normal tissues and cells with quantitative Real-time polymerase chain reaction. Kaplan-Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. Effect of FTH1P3 on the proliferation migration and invasion of OSCC cells was estimated by MTT, wound-healing, and transwell assays. Western blot was performed to investigate the effects of FTH1P3 on expression of PI3K/Akt/GSK3β-related molecules, and Wnt/β-catenin signaling components.
The expression level of FTH1P3 was significantly upregulated in OSCC tissues and cell lines. Higher expression of FTH1P3 in OSCC tissue was associated with T classification, N classification and TNM stage. Furthermore, Kaplan-Meier survival analysis showed that prognosis of patients with low FTH1P3 expression was much better than that of those with high expression. Cox regression analysis showed that FTH1P3 expression was an independent prognosis-predicting factor for OSCC patients. Loss-function assay showed that knockdown of FTH1P3 significantly suppressed the proliferation, migration and invasion of OSCC cells. Mechanistically, we found that knockdown of FTH1P3 significantly reduced the activation of PI3K/Akt/GSK3β/Wnt/β-catenin signaling.
We demonstrated that FTH1P3 acted as a tumor promoter by regulating PI3K/Akt/GSK3β/Wnt/β-catenin signaling and could represent a novel prognostic marker in OSCC patients.
越来越多的证据表明，长非编码 RNA（lncRNA）在肿瘤的发生和发展中发挥着重要作用。本研究旨在探讨铁蛋白重链 1 假基因 3（FTH1P3）在口腔鳞状细胞癌（OSCC）中的表达模式、临床意义和生物学功能。
我们通过定量实时聚合酶链反应评估了 FTH1P3 在 OSCC 组织、相邻正常组织和细胞中的表达水平。Kaplan-Meier 曲线和多变量 Cox 比例模型用于研究对临床结果的影响。通过 MTT、划痕愈合和 Transwell 测定评估 FTH1P3 对 OSCC 细胞增殖、迁移和侵袭的影响。Western blot 用于研究 FTH1P3 对 PI3K/Akt/GSK3β 相关分子和 Wnt/β-catenin 信号成分表达的影响。
FTH1P3 的表达水平在 OSCC 组织和细胞系中显著上调。OSCC 组织中 FTH1P3 的高表达与 T 分类、N 分类和 TNM 分期有关。此外，Kaplan-Meier 生存分析表明，FTH1P3 低表达的患者预后明显优于高表达的患者。Cox 回归分析表明，FTH1P3 表达是 OSCC 患者的独立预后预测因素。失活功能测定表明，FTH1P3 敲低显著抑制了 OSCC 细胞的增殖、迁移和侵袭。机制上，我们发现 FTH1P3 敲低显著降低了 PI3K/Akt/GSK3β/Wnt/β-catenin 信号的激活。
我们证明 FTH1P3 通过调节 PI3K/Akt/GSK3β/Wnt/β-catenin 信号发挥肿瘤促进作用，可作为 OSCC 患者的新型预后标志物。
