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.
近期，多种肿瘤抑制性微小核糖核酸（TS-miRs）在人类恶性肿瘤中被发现。本研究旨在鉴定口腔鳞状细胞癌（OSCC）中新型的TS-miRs。首先，我们分别将968种模拟人类成熟miRs的合成miRs转染至人OSCC细胞中，并通过WST-8实验评估这些细胞的生长情况。其中五种miR模拟物使细胞生长率显著降低至30%以下，而miR-1289模拟物在这些miRs中表现出最强的生长抑制效果。随后，我们利用小鼠模型评估了miR-1289的体内生长抑制作用。注射miR-1289模拟物-阿特胶原复合物显著减小了皮下异种移植的人OSCC肿瘤体积。接下来，我们通过逆转录定量PCR技术检测了miR-1289在OSCC组织中的表达情况。结果显示，miR-1289在OSCC组织中的表达水平显著低于邻近的正常口腔黏膜。此外，通过微阵列分析和Ingenuity通路分析（IPA）的miRNA靶点筛选，我们确定了15个基因为miR-1289的靶基因。在这些基因中，敲低镁转运蛋白1（MAGT1）在人OSCC细胞中引起了最为显著的细胞生长抑制。这些结果表明，miR-1289在OSCC中作为一种新型TS-miR发挥作用，并可能成为OSCC患者潜在的有效治疗工具。
MicroRNA-1289 Functions as a Novel Tumor Suppressor in Oral Squamous Cell Carcinoma
肿瘤(癌症)患者之家