| Title: |
Post-transcriptional Gene Regulation by MicroRNA-194 Promotes Neuroendocrine Transdifferentiation in Prostate Cancer |
| Authors: |
Fernandes, RC; Toubia, J; Townley, S; Hanson, AR; Dredge, BK; Pillman, KA; Bert, AG; Winter, JM; Iggo, R; Das, R; Obinata, D; Sandhu, S; Risbridger, GP; Taylor, RA; Lawrence, MG; Butler, LM; Zoubeidi, A; Gregory, PA; Tilley, WD; Hickey, TE; Goodall, GJ; Selth, LA |
| Publisher Information: |
CELL PRESS |
| Publication Year: |
2021 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
https://hdl.handle.net/11343/280222 |
| Availability: |
https://hdl.handle.net/11343/280222 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0 ; CC BY-NC-ND |
| Accession Number: |
edsbas.81AC9B48 |
| Database: |
BASE |