Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/105537
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Type: Journal article
Title: A ZEB1-miR-375-YAP1 pathway regulates epithelial plasticity in prostate cancer
Author: Selth, L.
Das, R.
Townley, S.
Coutinho, I.
Hanson, A.
Centenera, M.
Stylianou, N.
Sweeney, K.
Soekmadji, C.
Jovanovic, L.
Nelson, C.
Zoubeidi, A.
Butler, L.
Goodall, G.
Hollier, B.
Gregory, P.
Tilley, W.
Citation: Oncogene, 2017; 36(1):24-34
Publisher: Nature Publishing Group
Issue Date: 2017
ISSN: 0950-9232
1476-5594
Statement of
Responsibility: 
LA Selth, R Das, SL Townley, I Coutinho, AR Hanson, MM Centenera, N Stylianou, K Sweeney, C Soekmadji, L Jovanovic, CC Nelson, A Zoubeidi, LM Butler, GJ Goodall, BG Hollier, PA Gregory, and WD Tilley
Abstract: MicroRNA-375 (miR-375) is frequently elevated in prostate tumors and cell-free fractions of patient blood, but its role in genesis and progression of prostate cancer is poorly understood. In this study, we demonstrated that miR-375 is inversely correlated with epithelial–mesenchymal transition signatures (EMT) in clinical samples and can drive mesenchymal–epithelial transition (MET) in model systems. Indeed, miR-375 potently inhibited invasion and migration of multiple prostate cancer lines. The transcription factor YAP1 was found to be a direct target of miR-375 in prostate cancer. Knockdown of YAP1 phenocopied miR-375 overexpression, and overexpression of YAP1 rescued anti-invasive effects mediated by miR-375. Furthermore, transcription of the miR-375 gene was shown to be directly repressed by the EMT transcription factor, ZEB1. Analysis of multiple patient cohorts provided evidence for this ZEB1-miR-375-YAP1 regulatory circuit in clinical samples. Despite its anti-invasive and anti-EMT capacities, plasma miR-375 was found to be correlated with circulating tumor cells in men with metastatic disease. Collectively, this study provides new insight into the function of miR-375 in prostate cancer, and more broadly identifies a novel pathway controlling epithelial plasticity and tumor cell invasion in this disease.
Keywords: Epithelium
Cell Line, Tumor
Animals
Humans
Prostatic Neoplasms
Adaptor Proteins, Signal Transducing
Phosphoproteins
Transcription Factors
MicroRNAs
3' Untranslated Regions
Signal Transduction
Gene Expression
Gene Expression Regulation, Neoplastic
RNA Interference
Phenotype
Male
Proto-Oncogene Proteins c-met
Neoplastic Cells, Circulating
Epithelial-Mesenchymal Transition
Biomarkers
Zinc Finger E-box-Binding Homeobox 1
Rights: © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved
DOI: 10.1038/onc.2016.185
Grant ID: http://purl.org/au-research/grants/nhmrc/1083961
Appears in Collections:Aurora harvest 3
Medical Education Unit publications

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