Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong, Xi'an 710061, the People's Republic of China.
Cancer Cell Int. 2013 May 28;13(1):51. doi: 10.1186/1475-2867-13-51.
MicroRNAs (miRNAs) are a large group of negative gene regulators that potentially play a critical role in tumorigenesis. Increasing evidences indicate that miR-145 acts a tumor suppressor in numerous human cancers. However, its role in oral carcinogenesis remains poorly defined. The aim of this study is to determine expression levels of miR-145 in oral squamous cell carcinomas (OSCCs) and normal mucosa tissues, and explore its biological functions in OSCCs.
Reverse transcription quantitative real-time PCR (RT-qPCR) assay was used to evaluate expression levels of miR-145. The biological functions of miR-145 were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell invasion assay.
MiR-145 was frequently down-regulated in OSCCs compared with normal mucosa tissues. Restoring miR-145 expression in OSCC cells dramatically suppressed cell proliferation and colony formation, and induced G1 phase arrest and cell apoptosis. Importantly, our data showed that miR-145 downregulated the expression of c-Myc and Cdk6, which have previously been identified as two direct targets of miR-145.
Our data suggest that miR-145 exerts its tumor suppressor function by targeting c-Myc and Cdk6, leading to the inhibition of OSCC cell growth. MiR-145 rescue may thus be a rational for diagnostic and therapeutic applications in OSCC.
MicroRNAs（miRNAs）是一大类负向基因调控因子，它们在肿瘤发生中可能发挥关键作用。越来越多的证据表明，miR-145 在许多人类癌症中作为肿瘤抑制因子发挥作用。然而，其在口腔癌发生中的作用仍未明确。本研究旨在确定 miR-145 在口腔鳞状细胞癌（OSCCs）和正常黏膜组织中的表达水平，并探讨其在 OSCCs 中的生物学功能。
采用逆转录定量实时 PCR（RT-qPCR）检测 miR-145 的表达水平。通过细胞增殖和集落形成、细胞周期和凋亡以及细胞侵袭实验来确定 miR-145 的生物学功能。
miR-145 在 OSCCs 中较正常黏膜组织常下调。在 OSCC 细胞中恢复 miR-145 表达可显著抑制细胞增殖和集落形成，并诱导 G1 期阻滞和细胞凋亡。重要的是，我们的数据表明，miR-145 下调了 c-Myc 和 Cdk6 的表达，这两种蛋白先前已被鉴定为 miR-145 的两个直接靶标。
我们的数据表明，miR-145 通过靶向 c-Myc 和 Cdk6 发挥其肿瘤抑制功能，从而抑制 OSCC 细胞生长。miR-145 恢复可能是 OSCC 诊断和治疗应用的合理策略。
