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

Arch Oral Biol. 2020 Aug;116:104732. Epub 2020 Apr 24
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摘要


OBJECTIVE:The 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. DESIGN:Microarray 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. RESULTS:The 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. CONCLUSIONS:The 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.

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