MicroRNA-655 suppresses cell proliferation and invasion in oral squamous cell carcinoma by directly targeting metadherin and regulating the PTEN/AKT pathway

摘要

MicroRNAs (miRNAs) are important regulators of a variety of biological processes and their dysregulation is closely related to cancer formation and progression. Therefore, examination of aberrantly expressed miRNAs in oral squamous cell carcinoma (OSCC) may provide important clues for the diagnosis and treatment of patients with OSCC. The aim of the present study was to determine miRNA (miR)-655-3p expression in OSCC tissues and cell lines, and to investigate the biological roles and mechanisms of miR-655-3p associated with OSCC. Data from the present study indicated that miR-655 expression was significantly downregulated in human OSCC tissues and cell lines. Overexpression of miR-655 attenuated cell proliferation and invasion in OSCC in vitro. Mctadhcrin (MTDH) mRNA was predicted as a potential target of miR-655 by bioinformatics analysis, and this was confirmed by luciferase reporter assay, reverse transcription-quantitative polymerise chain reaction and western blot analysis. In OSCC tissues, MTDH was highly expressed and inversely correlated with miR-655 expression levels. MTDH overexpression reversed the inhibitory effects of miR-655 mimics in OSCC cells. Notably, the upregulation of miR-655 expression inhibited the activation of the phosphatase and tensin homolog (PTEN)/RAC-alpha serinelthreonine-protein kinase (AKT) pathway in OSCC cells. Therefore, these results may provide the first evidence that miR-655 targets MTDH to inhibit proliferation and invasion of OSCC by inhibiting PTEN/AKT signaling. Thus, the restoration of miR-655 expression may be a novel therapeutic strategy for patients with OSCC.