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Type: Journal article
Title: Combinatorial targeting by MicroRNAs co-ordinates post-transcriptional control of EMT
Author: Cursons, J.
Pillman, K.A.
Scheer, K.G.
Gregory, P.A.
Foroutan, M.
Hediyeh-Zadeh, S.
Toubia, J.
Crampin, E.J.
Goodall, G.J.
Bracken, C.P.
Davis, M.J.
Citation: Cell Systems, 2018; 7(1):77-91
Publisher: Cell Press
Issue Date: 2018
ISSN: 2405-4712
Statement of
Joseph Cursons, Katherine A. Pillman, Kaitlin G. Scheer, Philip A.Gregory, Momeneh Foroutan ... Gregory J.Goodall ... et al.
Abstract: MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression, functioning in part by facilitating the degradation of target mRNAs. They have an established role in controlling epithelial-mesenchymal transition (EMT), a reversible phenotypic program underlying normal and pathological processes. Many studies demonstrate the role of individual miRNAs using overexpression at levels greatly exceeding physiological abundance. This can influence transcripts with relatively poor targeting and may in part explain why over 130 different miRNAs are directly implicated as EMT regulators. Analyzing a human mammary cell model of EMT we found evidence that a set of miRNAs, including the miR-200 and miR-182/183 family members, co-operate in post-transcriptional regulation, both reinforcing and buffering transcriptional output. Investigating this, we demonstrate that combinatorial treatment altered cellular phenotype with miRNA concentrations much closer to endogenous levels and with less off-target effects. This suggests that co-operative targeting by miRNAs is important for their physiological function and future work classifying miRNAs should consider such combinatorial effects.
Keywords: epithelial-mesenchymal transition
exon-intron split analysis
post-transcriptional regulation
transforming growth factor β
Rights: © 2018 The Authors. Published by Elsevier Inc.
DOI: 10.1016/j.cels.2018.05.019
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