MicroRNA-345 functions as a tumor suppressor via targeting ZEB2 in oral squamous cell carcinoma

Abstract

ObjectiveThe objective of this study was to explore the role of miRNAs in OSCC and to identify potential novel biomarkers or therapeutic agents in OSCC treatment. DesignMicroarray analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to identify and verify differentially expressed miRNAs in OSCC tissues. The migration, invasion, proliferation and cell cycle of OSCC cells were analyzed to determine the function of miR-345 in OSCC development. Bioinformatics analysis and Dual-luciferase reporter assays were performed to identify and verify the target of miR-345. ResultsThe results showed a total of 17 miRNAs with significantly different expression in OSCC tissues (5 upregulated miRNAs and 12 downregulated miRNAs), including miR-345. The microarray results were also validated by qRT-PCR using 22 pairs of cancerous tissues and matched non-cancerous healthy samples. In particular, miR-345 expression was significantly lower in OSCC tissues. In addition, overexpression of miR-345 mimics in OSCC cells significantly inhibited their migration, invasion and proliferation while inducing cell cycle arrest in the G1 phase. Bioinformatics analysis predicted ZEB2 (zinc finger E-box-binding homeobox 2) as a potential target of miR-345, and luciferase reporter assays confirmed that miR-345 targeted ZEB2 through direct binding the 3′ untranslated region of ZEB2. Furthermore, miR-345 overexpression in OSCC reduced both mRNA and protein expression of ZEB2. ConclusionsThe results of this study indicated that miR-345 functions as a tumor suppressor to target ZEB2 in OSCC. These findings suggest that the miR-345/ZEB2 axis may be used as a potential therapeutic target in OSCC treatment.