Genome-wide identification of miR-200 targets reveals a regulatory network controlling cell invasion
Date
2014
Authors
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.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
EMBO Journal, 2014; 33(18):1979-2134
Statement of Responsibility
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
Conference Name
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.
School/Discipline
Dissertation Note
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Description
Published online 28.07.2014
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Rights
© 2014 The Authors