FBXW7 inhibited cell proliferation and invasion regulated by miR-27a through PI3K/AKT signaling pathway and epithelial-to-mesenchymal transition in oral squamous cell carcinoma

C. Li, X.-F. Lin, J.-N. Wang, X.-S. Ren

Department of Orthodontics, Jinan Stomatological Hospital, Jinan, China. jsgwrc979294@163.com

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• Oncology

OBJECTIVE: Our purpose was to detect the molecular mechanism of F-box and WD repeat domain containing 7 (FBXW7) in regulating cell growth and metastasis of oral squamous cell carcinoma (OSCC).

PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot were applied to calculate the messenger ribonucleic acid (mRNA) and protein levels of genes and miR-27a. The proliferation and invasive abilities were measured by methyl thiazolyl tetrazolium (MTT) and transwell assays. The. Kaplan-Meier method was conducted to evaluate the 5-year overall survival of oral squamous cell carcinoma patients.

RESULTS: FBXW7 was downregulated while miR-27a was upregulated in OSCC tissues and cells compared with the corresponding adjacent tissues. Downregulation of FBXW7 or upregulation of miR-27a in OSCC tissues predicted poor outcome of OSCC patients. FBXW7 suppressed the growth through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway in OSCC cell line HSC3. FBXW7 inhibited the invasion-mediated epithelial-mesenchymal transition (EMT) in HSC3 cells. The expression of FBXW7 was mediated by miR-27a by directly binding to the 3’-untranslated region (3’-UTR) of FBXW7 in HSC3 cells. MiR-27a reversed partial roles of FBXW7 on the proliferation and invasion in OSCC cells.

CONCLUSIONS: FBXW7 was mediated by miR-27a and could inhibit the proliferation through the PI3K/AKT pathway and invasion-mediated EMT in OSCC cell line. The newly identified miR-27a/FBXW7/PI3K/AKT axis provides novel insights into the pathogenesis of osCC.

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