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Type: Journal article
Title: Genome-wide identification of miR-200 targets reveals a regulatory network controlling cell invasion
Author: Bracken, C.P.
Li, X.
Wright, J.A.
Lawrence, D.
Pillman, K.A.
Salmanidis, M.
Anderson, M.A.
Dredge, B.K.
Gregory, P.A.
Tsykin, A.
Neilsen, C.
Thomson, D.
Bert, A.
Leerberg, J.
Yap, A.
Jensen, K.
Khew-Goodall, Y.
Goodall, G.
Citation: The EMBO Journal, 2014; 33(18):1979-2134
Publisher: EMBO Press
Issue Date: 2014
ISSN: 1460-2075
Statement of
Cameron P Bracken, Xiaochun Li, Josephine A Wright, David M Lawrence, Katherine A Pillman, Marika Salmanidis, Matthew A Anderson, B Kate Dredge, Philip A Gregory, Anna Tsykin, Corine Neilsen, Daniel W Thomson, Andrew G Bert, Joanne M Leerberg, Alpha S Yap, Kirk B Jensen, Yeesim Khew‐Goodall, Gregory J Goodall
Abstract: The microRNAs of the miR‐200 family maintain the central characteristics of epithelia and inhibit tumor cell motility and invasiveness. Using the Ago‐HITS‐CLIP technology for transcriptome‐wide identification of direct microRNA targets in living cells, along with extensive validation to verify the reliability of the approach, we have identified hundreds of miR‐200a and miR‐200b targets, providing insights into general features of miRNA target site selection. Gene ontology analysis revealed a predominant effect of miR‐200 targets in widespread coordinate control of actin cytoskeleton dynamics. Functional characterization of the miR‐200 targets indicates that they constitute subnetworks that underlie the ability of cancer cells to migrate and invade, including coordinate effects on Rho‐ROCK signaling, invadopodia formation, MMP activity, and focal adhesions. Thus, the miR‐200 family maintains the central characteristics of the epithelial phenotype by acting on numerous targets at multiple levels, encompassing both cytoskeletal effectors that control actin filament organization and dynamics, and upstream signals that locally regulate the cytoskeleton to maintain cell morphology and prevent cell migration.
Keywords: cytoskeleton; HITS-CLIP; invadopodia; microRNA; miR-200
Description: Published online 28.07.2014
Rights: © 2014 The Authors
RMID: 0030008745
DOI: 10.15252/embj.201488641
Grant ID:
Appears in Collections:Molecular and Biomedical Science publications

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