miR-1 suppresses the growth of esophageal squamous cell carcinoma in vivo and in vitro through the downregulation of MET, cyclin D1 and CDK4 expression
miR-1 suppresses the growth of esophageal squamous cell carcinoma in vivo and in vitro through the downregulation of MET, cyclin D1 and CDK4 expression
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DOI：
10.3892/ijmm.2016.2619
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发表时间：
2016-07-01
影响因子：
5.4
通讯作者：
Zhao, Yaping
中科院分区：
文献类型：
--
作者：
Jiang, Sen;Zhao, Chao;Zhao, Yaping
几种异常的 microRNA（miRNA 或 miR）与在中国广泛流行的食管癌（EC）有关。然而，它们在 EC 肿瘤发生中的作用尚未完全阐明。在本研究中，我们使用 RT-qPCR 确定，与邻近的非肿瘤组织相比，食管鳞状细胞癌 (ESCC) 组织中 miR-1 表达下调，并使用 ESCC 细胞系证实了这一点。使用裸鼠异种移植模型，我们证实miR-1的重新表达显着抑制ESCC肿瘤的生长。四唑试验和台盼蓝排除试验显示，miR-1 抑制 ESCC 细胞增殖并增加细胞凋亡，而 miR-1 的沉默促进细胞增殖并减少细胞凋亡，表明 miR-1 是一种新型肿瘤抑制因子。为了阐明 miR-1 在 ESCC 中作用的分子机制，我们使用生物信息学工具研究了假定的靶点。 MET、细胞周期蛋白 D1 和细胞周期蛋白依赖性激酶 4 (CDK4) 参与肝细胞生长因子 (HGF)/MET 信号通路，被发现是 miR-1 的靶标。 ESCC 细胞中 miR-1 表达与 MET、cyclin D1 和 CDK4 表达呈负相关。 miR-1 直接靶向 MET、细胞周期蛋白 D1 和 CDK4，抑制 ESCC 细胞生长。新发现的miR-1/MET/cyclin D1/CDK4轴为ESCC发病机制的分子机制提供了新的见解，并为ESCC的诊断和治疗提供了新的策略。
Several aberrant microRNAs (miRNAs or miRs) have been implicated in esophageal cancer (EC), which is widely prevalent in China. However, their role in EC tumorigenesis has not yet been fully elucidated. In the present study, we determined that miR-1 was downregulated in esophageal squamous cell carcinoma (ESCC) tissues compared with adjacent non-neoplastic tissues using RT-qPCR, and confirmed this using an ESCC cell line. Using a nude mouse xenograft model, we confirmed that the re-expression of miR-1 significantly inhibited ESCC tumor growth. A tetrazolium assay and a trypan blue exclusion assay revealed that miR-1 suppressed ESCC cell proliferation and increased apoptosis, whereas the silencing of miR-1 promoted cell proliferation and decreased apoptosis, suggesting that miR-1 is a novel tumor suppressor. To elucidate the molecular mechanisms of action of miR-1 in ESCC, we investigated putative targets using bioinformatics tools. MET, cyclin D1 and cyclin-dependent kinase 4 (CDK4), which are involved in the hepatocyte growth factor (HGF)/MET signaling pathway, were found to be targets of miR-1. miR-1 expression inversely correlated with MET, cyclin D1 and CDK4 expression in ESCC cells. miR-1 directly targeted MET, cyclin D1 and CDK4, suppressing ESCC cell growth. The newly identified miR-1/MET/cyclin D1/CDK4 axis provides new insight into the molecular mechanisms of ESCC pathogenesis and indicates a novel strategy for the diagnosis and treatment of ESCC.