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Type: Journal article
Title: Post-transcriptional gene regulation by microRNA-194 promotes neuroendocrine transdifferentiation in prostate cancer
Author: Fernandes, R.C.
Toubia, J.
Townley, S.
Hanson, A.R.
Dredge, B.K.
Pillman, K.A.
Bert, A.G.
Winter, J.M.
Iggo, R.
Das, R.
Obinata, D.
MURAL investigators
Sandhu, S.
Risbridger, G.P.
Taylor, R.A.
Lawrence, M.G.
Butler, L.M.
Zoubeidi, A.
Gregory, P.A.
Tilley, W.D.
et al.
Citation: Cell Reports, 2021; 34(1):1-17
Publisher: Elsevier
Issue Date: 2021
ISSN: 2211-1247
Statement of
Rayzel C. Fernandes, John Toubia, Scott Townley, Adrienne R. Hanson, B. Kate Dredge, Katherine A. Pillman, Andrew G. Bert, Jean M. Winter, Richard Iggo, Rajdeep Das, Daisuke Obinata, MURAL investigators, Shahneen Sandhu, Gail P. Risbridger, Renea A. Taylor, Mitchell G. Lawrence, Lisa M. Butler, Amina Zoubeidi, Philip A. Gregory, Wayne D. Tilley, Theresa E. Hickey, Gregory J. Goodall, and Luke A. Selth
Abstract: Potent therapeutic inhibition of the androgen receptor (AR) in prostate adenocarcinoma can lead to the emergence of neuroendocrine prostate cancer (NEPC), a phenomenon associated with enhanced cell plasticity. Here, we show that microRNA-194 (miR-194) is a regulator of epithelial-neuroendocrine transdifferentiation. In clinical prostate cancer samples, miR-194 expression and activity were elevated in NEPC and inversely correlated with AR signaling. miR-194 facilitated the emergence of neuroendocrine features in prostate cancer cells, a process mediated by its ability to directly target a suite of genes involved in cell plasticity. One such target was FOXA1, which encodes a transcription factor with a vital role in maintaining the prostate epithelial lineage. Importantly, a miR-194 inhibitor blocked epithelial-neuroendocrine transdifferentiation and inhibited the growth of cell lines and patient-derived organoids possessing neuroendocrine features. Overall, our study reveals a post-transcriptional mechanism regulating the plasticity of prostate cancer cells and provides a rationale for targeting miR-194 in NEPC.
Keywords: MiR-194; microRNA; prostate cancer; neuroendocrine prostate cancer; FOXA1; transdifferentiation; lineage plasticity; post-transcriptional gene regulation
Rights: © 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (
DOI: 10.1016/j.celrep.2020.108585
Grant ID:
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