miR-200a-mediated downregulation of ZEB2 and CTNNB1 differentially inhibits nasopharyngeal carcinoma cell growth, migration and invasion
miR-200a-mediated downregulation of ZEB2 and CTNNB1 differentially inhibits nasopharyngeal carcinoma cell growth, migration and invasion
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DOI：
10.1016/j.bbrc.2009.11.093
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发表时间：
2010-01-01
影响因子：
3.1
通讯作者：
Lin, Marie C.
中科院分区：
文献类型：
--
作者：
Xia, Hongping;Ng, Samuel S.;Lin, Marie C.
鼻咽癌（Nasopharyngeal carcinoma，NPC）是一种起源于鼻咽部的高转移、侵袭性恶性肿瘤。在东南亚、中东和北非广泛流行。尽管病毒、饮食和遗传因素与NPC有关，但其发病机制的分子基础尚未明确。基于最近的microRNA（miRNA）微阵列研究显示miR-200在NPC中下调，我们进一步研究了miR-200 a在NPC癌变过程中的作用。200 a的表达水平随着一组NPC细胞系的分化程度而增加。即未分化的C666-1、高分化的CNE-1、低分化的CNE-2和HNE 1细胞通过一系列功能获得和功能丧失的研究，我们发现过表达miR-200 a抑制C666-1细胞的生长、迁移和侵袭，而其敲除则刺激CNE-1细胞的这些过程。此外，我们进一步鉴定了ZEB 2和CTNNB 1作为miR-200 a的功能性下游靶标。有趣的是，ZEB 2的敲低仅阻碍NPC细胞迁移和侵袭，而CTNNB 1的抑制仅抑制NPC细胞生长。提示miR-200 a对NPC细胞生长、迁移和侵袭的抑制作用是由不同的靶点和途径介导的我们的研究结果揭示了miR-200 a作为NPC致癌的调节因子的重要作用，并为基于miRNA的NPC治疗提供了潜在的候选者（C）2009 Elsevier Inc版权所有
Nasopharyngeal carcinoma (NPC), a highly metastatic and invasive malignant tumor originating from the nasopharynx. is widely prevalent in Southeast Asia, the Middle East and North Africa Although viral, dietary and genetic factors have been implicated in NPC, the molecular basis of its pathogenesis is not well defined Based on a recent microRNA (miRNA) microarray study showing miR-200 downregulation in NPC, we further investigated the role of miR-200a in NPC carcinogenesis We found that the endogenous miR-200a expression level increases with the degree of differentiation in a panel of NPC cell lines. namely undifferentiated C666-1, high-differentiated CNE-1, and low-differentiated CNE-2 and HNE1 cells By a series of gain-of-function and loss-of-function studies, we showed that over-expression of miR-200a inhibits C666-1 cell growth, migration and invasion, whereas its knock-clown Stimulates these processes in CNE-1 cells In addition, we further identified ZEB2 and CTNNB1 as the functional downstream targets of miR-200a Interestingly, knock-down of ZEB2 solely impeded NPC cell migration and invasion, whereas CTNNB1 Suppression Only inhibited NPC cell growth. suggesting that the inhibitory effects of miR-200a on NPC cell growth, migration and invasion are mediated by distinct targets and pathways Our results reveal the important role of miR-200a as a regulatory factor of NPC carcinogenesis and a potential candidate for miRNA-based therapy against NPC (C) 2009 Elsevier Inc All rights reserved