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MicroRNA 135a Suppresses Lymph Node Metastasis through Down-Regulation of ROCK1 in Early Gastric Cancer
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MicroRNA 135a Suppresses Lymph Node Metastasis through Down-Regulation of ROCK1 in Early Gastric Cancer
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Journal Article
MicroRNA 135a Suppresses Lymph Node Metastasis through Down-Regulation of ROCK1 in Early Gastric Cancer
2014
Overview
MicroRNAs (miRNAs) play a critical role in gastric cancer progression and metastasis. This study investigated the role of miRNA-135a in early gastric cancer (EGC) including lymph node (LN) metastasis. We examined the correlation between miRNA-135a expression and clinical outcomes in 59 patients who underwent surgery for EGC. Using gastric cancer cell lines, we performed functional and target gene analyses. miRNA-135a expression was down-regulated in 33.9% of patients. These patients showed a significantly more advanced stage (TNM stage ≥ IB, 35.0% vs. 12.8%, p = 0.045) and higher rate of LN metastasis (30.0% vs. 5.1%, p = 0.014) than those with up-regulation of miRNA-135a expression. In a multivariate analysis, down-regulation of miRNA-135a was an independent risk factor for LN metastasis (adjusted odds ratio, 8.04; 95% confidence interval, 1.08-59.81; p = 0.042). Functional analyses using gastric cancer cell lines showed that miRNA-135a suppressed cell viability, epithelial-mesenchymal transition, cell invasion, and migration. ROCK1 was a target of miRNA-135a and its expression was inversely correlated to that of miRNA-135a. ROCK1 expression was significantly increased in EGC patients with LN metastasis than in those without LN metastasis. Our results confirm the tumor-suppressive role of miRNA-135a, and demonstrate its role in LN metastasis in EGC. miRNA-135a and its target gene ROCK1 may be novel therapeutic and prognostic targets for EGC.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Aged
/ Analysis
/ Biology
/ Cancer
/ Carcinoma, Signet Ring Cell - diagnosis
/ Carcinoma, Signet Ring Cell - genetics
/ Carcinoma, Signet Ring Cell - metabolism
/ Carcinoma, Signet Ring Cell - pathology
/ Epithelial-Mesenchymal Transition
/ Female
/ Gene Expression Regulation, Neoplastic
/ Genes
/ Humans
/ Kinases
/ Lymph
/ Male
/ Medicine
/ MicroRNA
/ miRNA
/ Patients
/ rho-Associated Kinases - genetics
/ rho-Associated Kinases - metabolism
/ RNA
/ Stomach Neoplasms - diagnosis
/ Stomach Neoplasms - genetics
/ Stomach Neoplasms - metabolism
/ Stomach Neoplasms - pathology
/ Studies
/ Surgery
