Increased expression of lncRNA FTH1P3 promotes oral squamous cell carcinoma cells migration and invasion by enhancing PI3K/Akt/GSK3b/ Wnt/β-catenin signaling.

OBJECTIVE: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). PATIENTS AND METHODS: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. RESULTS: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. CONCLUSIONS: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.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}