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Downregulated MicroRNA-200a in Meningiomas Promotes Tumor Growth by Reducing E-Cadherin and Activating the Wnt/-Catenin Signaling Pathway


Saydam, O; Shen, Y; Würdinger, T; Senol, O; Boke, E; James, M F; Tannous, B A; Stemmer-Rachamimov, A O; Yi, M; Stephens, R M; Fraefel, C; Gusella, J F; Krichevsky, A M; Breakefield, X O (2009). Downregulated MicroRNA-200a in Meningiomas Promotes Tumor Growth by Reducing E-Cadherin and Activating the Wnt/-Catenin Signaling Pathway. Molecular and Cellular Biology, 29(21):5923-5940.

Abstract

Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, are usually benign, and are frequently associated with neurofibromatosis type 2. Here, we define a typical human meningioma microRNA (miRNA) profile and characterize the effects of one downregulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Upregulation of miR-200a decreased the expression of transcription factors ZEB1 and SIP1, with consequent increased expression of E-cadherin, an adhesion protein associated with cell differentiation. Downregulation of miR-200a in meningiomas and arachnoidal cells resulted in
increased expression of -catenin and cyclin D1 involved in cell proliferation. miR-200a was found to directly
target -catenin mRNA, thereby inhibiting its translation and blocking Wnt/-catenin signaling, which is frequently involved in cancer. A direct correlation was found between the downregulation of miR-200a and the upregulation of -catenin in human meningioma samples. Thus, miR-200a appears to act as a multifunctional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and Wnt/-catenin signaling pathways. This reveals a previously unrecognized signaling cascade involved in meningioma tumor development and highlights a novel molecular interaction between miR-200a and Wnt signaling, thereby providing
insights into novel therapies for meningiomas.

Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, are usually benign, and are frequently associated with neurofibromatosis type 2. Here, we define a typical human meningioma microRNA (miRNA) profile and characterize the effects of one downregulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Upregulation of miR-200a decreased the expression of transcription factors ZEB1 and SIP1, with consequent increased expression of E-cadherin, an adhesion protein associated with cell differentiation. Downregulation of miR-200a in meningiomas and arachnoidal cells resulted in
increased expression of -catenin and cyclin D1 involved in cell proliferation. miR-200a was found to directly
target -catenin mRNA, thereby inhibiting its translation and blocking Wnt/-catenin signaling, which is frequently involved in cancer. A direct correlation was found between the downregulation of miR-200a and the upregulation of -catenin in human meningioma samples. Thus, miR-200a appears to act as a multifunctional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and Wnt/-catenin signaling pathways. This reveals a previously unrecognized signaling cascade involved in meningioma tumor development and highlights a novel molecular interaction between miR-200a and Wnt signaling, thereby providing
insights into novel therapies for meningiomas.

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115 citations in Web of Science®
117 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Virology
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:November 2009
Deposited On:20 Nov 2009 09:33
Last Modified:05 Apr 2016 13:32
Publisher:American Society for Microbiology
ISSN:0270-7306
Additional Information:Copyright: American Society for Microbiology
Publisher DOI:https://doi.org/10.1128/MCB.00332-09
Permanent URL: https://doi.org/10.5167/uzh-23857

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