MiR-29c suppresses invasion and metastasis by targeting TIAM1 in nasopharyngeal carcinoma
MiR-29c suppresses invasion and metastasis by targeting TIAM1 in nasopharyngeal carcinoma
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MiR-29c通过靶向TIAM1抑制鼻咽癌的侵袭和转移
DOI：
10.1016/j.canlet.2012.10.032
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发表时间：
2013-02-28
期刊：
影响因子：
9.7
通讯作者：
Ma, Jun
中科院分区：
文献类型：
--
作者：
Liu, Na;Tang, Ling-Long;Ma, Jun
基于微阵列分析，我们先前报道了miR-29 c在鼻咽癌（NPC）中显著下调。然而，关于miR-29 c失调在NPC发生和发展中的作用和分子作用机制知之甚少。定量RT-PCR结果显示，miR-29 c在鼻咽癌细胞系和临床标本中表达显著下调。创伤愈合、Transwell迁移和肺转移实验表明，miR-29 c的异位表达在体外可抑制NPC细胞的迁移和侵袭，在体内可抑制肺转移的形成。利用荧光素酶报告基因分析、定量RT-PCR和Western blotting证实T细胞淋巴瘤侵袭和转移1（TIAM 1）是miR-29 c的靶基因。TIAM 1的异位表达显著促进了稳定过表达miR-29 c的SUNE-1细胞系的迁移和侵袭。应用免疫组化方法分析217例鼻咽癌患者中TIAM 1的表达及其与预后的关系。引人注目的是，TIAM 1高表达患者的总体无病生存率和无远处转移生存率均低于TIAM 1低表达患者。多因素考克斯回归分析显示，TIAM 1可作为鼻咽癌的独立预后因素。新发现的miR-29 c/TIAM 1通路进一步阐明了调控鼻咽癌侵袭和转移的分子机制，可能为鼻咽癌患者的预后和治疗提供新的策略。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Based on microarray analysis, we previously reported that miR-29c is significantly downregulated in nasopharyngeal carcinoma (NPC). However, little is known about the effect and molecular mechanisms of action of miR-29c deregulation during the development and progression of NPC. Quantitative RT-PCR demonstrated that miR-29c was significantly downregulated in NPC cell lines and clinical specimens. Wound healing, Transwell migration and lung metastasis assays demonstrated that ectopic expression of miR-29c inhibited NPC cell migration and invasion in vitro and suppressed the formation of lung metastases in vivo. T cell lymphoma invasion and metastasis 1 (TIAM1) was confirmed as a miR-29c target gene using luciferase reporter assays, quantitative RT-PCR and Western blotting. Ectopic expression of TIAM1 significantly promoted the migration and invasion of SUNE-1 cell line stably overexpressing miR-29c. The prognostic value of TIAM1 was analyzed in 217 NPC patients using immunohistochemistry. Strikingly, patients with high TIAM1 expression had poorer overall, disease-free and distant metastasis-free survival than patients with low TIAM1 expression. Furthermore, multivariate Cox regression analysis revealed that TIAM1 could serve as an independent prognostic factor in NPC. The newly identified miR-29c/TIAM1 pathway further elucidates the molecular mechanisms regulating invasion and metastasis in NPC, and may provide novel prognostic and treatment strategies for NPC patients. (C) 2012 Elsevier Ireland Ltd. All rights reserved.