title: Genome-wide identification of miR-200 targets reveals a regulatory network controlling cell invasion.
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.
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors: Cameron P
authors: CP
authors: Bracken
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia.
authors: Xiaochun
authors: X
authors: Li
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia.
authors: Josephine A
authors: JA
authors: Wright
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia.
authors: David M
authors: DM
authors: Lawrence
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia.
authors: Katherine A
authors: KA
authors: Pillman
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia.
authors: Marika
authors: M
authors: Salmanidis
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia.
authors: Matthew A
authors: MA
authors: Anderson
authors: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia.
authors: B Kate
authors: BK
authors: Dredge
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors: Philip A
authors: PA
authors: Gregory
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia.
authors: Anna
authors: A
authors: Tsykin
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia.
authors: Corine
authors: C
authors: Neilsen
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia.
authors: Daniel W
authors: DW
authors: Thomson
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia.
authors: Andrew G
authors: AG
authors: Bert
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience University of Queensland, St Lucia, Brisbane, Qld, Australia.
authors: Joanne M
authors: JM
authors: Leerberg
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience University of Queensland, St Lucia, Brisbane, Qld, Australia.
authors: Alpha S
authors: AS
authors: Yap
authors: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia.
authors: Kirk B
authors: KB
authors: Jensen
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia yeesim.khew-goodall@health.sa.gov.au greg.goodall@health.sa.gov.au.
authors: Yeesim
authors: Y
authors: Khew-Goodall
authors: Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia yeesim.khew-goodall@health.sa.gov.au greg.goodall@health.sa.gov.au.
authors: Gregory J
authors: GJ
authors: Goodall
mesh_terms: D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs
keywords: HITS‐CLIP; cytoskeleton; invadopodia; miR‐200; microRNA