MicroRNA-1289 Functions as a Novel Tumor Suppressor in Oral Squamous Cell Carcinoma

SIMPLE SUMMARY: Tumor-suppressive microRNAs (TS-miRs) play an important role in human malignancies, such as oral squamous cell carcinoma (OSCC). Five such synthetic miRs mimicking human mature miRs were identified in this study. These molecules targeted OSCC cells and significantly reduced their growth. Of these, miR-1289 had the strongest effect, and the administration of an miR-1289 mimic/atelocollagen complex significantly reduced the size of OSCC tumors in vivo. The expression of miR-1289 was also significantly reduced in OSCC tissues. Therefore, identifying genes targeted by miRs, such as magnesium transporter 1 (MAGT1) that is targeted by miR-1289, can be an important therapeutic tool against malignancies like OSCC. ABSTRACT: Recently, numerous tumor-suppressive microRNAs (TS-miRs) have been identified in human malignancies. Here, we attempted to identify novel TS-miRs in oral squamous cell carcinoma (OSCC). First, we transfected human OSCC cells individually with 968 synthetic miRs mimicking human mature miRs individually, and the growth of these cells was evaluated using the WST-8 assay. Five miR mimics significantly reduced the cell growth rate by less than 30%, and the miR-1289 mimic had the most potent growth inhibitory effect among these miRs. Subsequently, we assessed the in vivo growth-inhibitory effects of miR-1289 using a mouse model. The administration of the miR-1289 mimic–atelocollagen complex significantly reduced the size of subcutaneously xenografted human OSCC tumors. Next, we investigated the expression of miR-1289 in OSCC tissues using reverse transcription–quantitative PCR. The expression level of miR-1289 was significantly lower in OSCC tissues than in the adjacent normal oral mucosa. Furthermore, 15 genes were identified as target genes of miR-1289 via microarray and Ingenuity Pathway Analysis (IPA) microRNA target filtering. Among these genes, the knockdown of magnesium transporter 1 (MAGT1) resulted in the most remarkable cell growth inhibition in human OSCC cells. These results suggested that miR-1289 functions as a novel TS-miR in OSCC and may be a useful therapeutic tool for patients with OSCC.