microRNA-92a Promotes Lymph Node Metastasis of Human Esophageal Squamous Cell Carcinoma via E-Cadherin

被引:134
作者
Chen, Zhao-li [1 ]
Zhao, Xiao-hong [1 ]
Wang, Ji-wen [1 ]
Li, Bao-zhong [1 ]
Wang, Zhen [1 ]
Sun, Jian [1 ]
Tan, Feng-wei [1 ]
Ding, Da-peng [1 ]
Xu, Xiao-hui [1 ]
Zhou, Fang [1 ]
Tan, Xiao-gang [1 ]
Hang, Jie [1 ]
Shi, Su-sheng [2 ,3 ]
Feng, Xiao-li [2 ,3 ]
He, Jie [1 ]
机构
[1] Peking Union Med Coll, Dept Thorac Surg, Beijing 100021, Peoples R China
[2] Peking Union Med Coll, Dept Pathol, Beijing 100021, Peoples R China
[3] Chinese Acad Med Sci, Beijing 100021, Peoples R China
基金
北京市自然科学基金;
关键词
CANCER METASTASIS; MIR-17-92; CLUSTER; PATIENT SURVIVAL; TUMOR INVASION; EXPRESSION; DIFFERENTIATION; ADENOCARCINOMA; AMPLIFICATION; DEREGULATION; POLYCISTRON;
D O I
10.1074/jbc.M110.165654
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and play important roles in tumor initiation and progression. Recently, we examined the global miRNA expression profile of esophageal squamous cell carcinoma (ESCC) and demonstrated that miR-92a was highly expressed in tumor tissues. In this study, we found that the up-regulation of miR-92a was significantly correlated with the status of lymph node metastasis and TNM stage in 107 ESCC patients. Moreover, the up-regulation of miR-92a was associated with poor survival of ESCC patients and might be used as an independent prognostic factor. Next, we investigated the role and mechanism of miR-92a in ESCC cells, and found that miR-92a modulated the migration and invasion but not apoptosis and proliferation of ESCC cells in vitro. We further demonstrated that miR-92a directly targeted the CDH1 3'-UTR and repressed the expression of CDH1, a tumor metastasis suppressor. In addition, restoring of miR-92a-resistant CDH1 expression in miR-92a-overexpression cells recovered the pro-metastasis activity of miR-92a. Taken together, we demonstrated that miR-92a promotes ESCC cell migration and invasion at least partially via suppression of CDH1 expression, and patients with up-regulated miR-92a are prone to lymph node metastasis and thus have poor prognosis.
引用
收藏
页码:10725 / 10734
页数:10
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