miR-200a-mediated downregulation of ZEB2 and CTNNB1 differentially inhibits nasopharyngeal carcinoma cell growth, migration and invasion

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...

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Veröffentlicht in:Biochemical and biophysical research communications 2010-01, Vol.391 (1), p.535-541
Hauptverfasser: Xia, Hongping, Ng, Samuel S., Jiang, Songshan, Cheung, William K.C., Sze, Johnny, Bian, Xiu-Wu, Kung, Hsiang-fu, Lin, Marie C.
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container_end_page 541
container_issue 1
container_start_page 535
container_title Biochemical and biophysical research communications
container_volume 391
creator Xia, Hongping
Ng, Samuel S.
Jiang, Songshan
Cheung, William K.C.
Sze, Johnny
Bian, Xiu-Wu
Kung, Hsiang-fu
Lin, Marie C.
description 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-down 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.
doi_str_mv 10.1016/j.bbrc.2009.11.093
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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-down 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. 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subjects Base Sequence
beta Catenin - genetics
Carcinoma - genetics
Carcinoma - metabolism
Carcinoma - pathology
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Cell Transformation, Neoplastic - pathology
Down-Regulation
Gene Expression Regulation, Neoplastic
Homeodomain Proteins - genetics
Humans
Invasion
microRNA
MicroRNAs - genetics
MicroRNAs - physiology
Migration
Nasopharyngeal carcinoma
Nasopharyngeal Neoplasms - genetics
Nasopharyngeal Neoplasms - metabolism
Nasopharyngeal Neoplasms - pathology
Neoplasm Invasiveness
Repressor Proteins - genetics
Zinc Finger E-box Binding Homeobox 2
β-catenin
title miR-200a-mediated downregulation of ZEB2 and CTNNB1 differentially inhibits nasopharyngeal carcinoma cell growth, migration and invasion
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