MiR-181d functions as a potential tumor suppressor in oral squamous cell carcinoma by targeting K-ras.

ABSTRACT

Oral squamous cell carcinoma (OSCC) is one of the most frequent carcinomas all over the world, and the mechanism of its progression remains poorly understood. MicroRNAs have been found to play pivotal roles in many cancers including OSCC. However, the detailed roles of miRNAs in OSCC remain to be fully elucidated. In this study, we aimed to investigate the role of miR-181d in the progression of OSCC and to further elucidate its possible regulatory mechanism. Differentially expressed miRNAs between OSCC tissues and adjacent normal tissues were identified by microarray and validated using quantitative reverse transcription PCR (qRT-PCR). Moreover, the effects of miR-181d on the cell viability and apoptosis were investigated. In addition, a direct target of miR-181a, K-ras was assessed by the luciferase reporter assay and western blot. K-ras was overexpressed to evaluate its reverse effect on miR-181d mediated tumor suppression in OSCC. A panel of 54 differentially expressed miRNAs was identified by microRNA array. Among them, miR-181d was showed to be significantly downregulated. We also found that miR-181d lowly expressed in 20 pairs of OSCC tissues and four cell lines compared with that in adjacent normal tissues and human normal oral keratinocyte cells. In vitro assays showed that upregulation of miR-181d markedly decreased cell viability and increased OSCC cell apoptosis. Furthermore, we demonstrated that K-ras was a target of miR-181d and there was a negative correlation between miR-181d and K-ras expression in OSCC tissues. Importantly, overexpression of K-ras reversed the inhibitory effects of miR-181d mimics on OSCC cells. miR-181d functions as an OSCC suppressor by targeting K-ras oncogene. Thus, miR-181d may serve as a novel therapeutic target for treating OSCC.