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

• Published in: The Journal of biological chemistry Vol. 286; no. 12; pp. 10725 - 10734
• Main Authors: Chen, Zhao-li, Zhao, Xiao-hong, Wang, Ji-wen, Li, Bao-zhong, Wang, Zhen, Sun, Jian, Tan, Feng-wei, Ding, Da-peng, Xu, Xiao-hui, Zhou, Fang, Tan, Xiao-gang, Hang, Jie, Shi, Su-sheng, Feng, Xiao-li, He, Jie
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.03.2011; American Society for Biochemistry and Molecular Biology
• Subjects: Antigens, CD; Cadherins - biosynthesis; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Cell Migration; Cell Movement; E-Cadherin; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - mortality; Esophageal Neoplasms - pathology; Esophageal Squamous Cell Caricinoma; Female; Gene Expression Regulation, Neoplastic; Humans; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphatic Metastasis; Male; MicroRNA; MicroRNAs - biosynthesis; Migration and Invasion; Molecular Bases of Disease; Neoplasm Invasiveness; Neoplasm Staging; RNA, Neoplasm - biosynthesis; Survival Rate; Tumor Cells, Cultured; Tumor Marker; Tumor Metastases; Tumor Suppressor; Cell Migration; MicroRNA; Migration and Invasion; E-Cadherin; Tumor Metastases; Esophageal Squamous Cell Caricinoma; Tumor Marker; Tumor Suppressor
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.165654

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.