Metastasis seriously affects the prognosis of patients with oral squamous cell carcinoma (OSCC); however, the precise mechanism remains poorly understood.
microRNA (miRNA) array analysis of four cell lines was used to identify candidate miRNAs. The Cancer Genome Atlas (TCGA) database was used to verify the relationship between candidate miRNAs and OSCC metastasis. Transwell chambers and mouse model experiments were used to analyze OSCC cell migration and invasion abilities in vitro and in vivo. Additionally, bioinformatics and a dual luciferase reporter assay were used to identify selected miRNA target genes. A multicenter clinical cohort of 250 patients with OSCC was set up to evaluate the diagnostic and predicted value of the target genes. Finally, the molecular mechanism of a selected miRNA regulating OSCC metastasis was further explored.
miR-223 expression was found to be negatively correlated with OSCC cell invasion and migration abilities. TCGA database data confirmed the relationship between miR-223 expression and OSCC metastasis. Functional experiments indicated that overexpression of miR-223 could decrease the metastasis ability of OSCC cells, while decreasing its expression level led to the enhancement of OSCC metastasis. Bioinformatics and a dual-luciferase reporter assay identified that miR-223 directly targets transcription factor 7-like 2 (TCF7L2). Additionally, TCF7L2 was shown to be negatively correlated with patient metastasis and survival.
miR-223 regulates OSCC invasion and metastasis by directly targeting TCF7L2 and potentiating the Wnt/β-catenin signaling pathway. These findings demonstrate the versatile role of miR-223 in carcinogenesis. miR-223 might serve as an attractive OSCC metastasis intervention target.
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