Journal article
Post-transcriptional Gene Regulation by MicroRNA-194 Promotes Neuroendocrine Transdifferentiation in Prostate Cancer
RC Fernandes, J Toubia, S Townley, AR Hanson, BK Dredge, KA Pillman, AG Bert, JM Winter, R Iggo, R Das, D Obinata, S Sandhu, GP Risbridger, RA Taylor, MG Lawrence, LM Butler, A Zoubeidi, PA Gregory, WD Tilley, TE Hickey Show all
Cell Reports | CELL PRESS | Published : 2021
Abstract
Neuroendocrine prostate cancer is an aggressive disease subtype associated with poor patient outcome. Fernandes et al. demonstrate that a microRNA, miR-194, promotes the emergence of neuroendocrine features in prostate cancer cells by targeting genes that regulate epithelial-neuroendocrine plasticity. Inhibiting miR-194 suppresses the growth of neuroendocrine prostate cancer models.
Grants
Awarded by National Human Genome Research Institute
Funding Acknowledgements
This work was supported by the National Health and Medical Research Council of Australia (1121057 to W.D.T., L.A.S., R.A.T., and G.P.R.; 1083961 to L.A.S., W.D.T., G.J.G., and P.A.G.; 1138242 to G.P.R., W.D.T., L.A.S., and M.G.L.; 1002648 to G.P.R.; 1118170 to G.J.G.) and Cancer Council South Australia (1185012 to L.A.S.). L.A.S., L.M.B., and P.A.G. are supported by Principal Cancer Research Fellowships awarded by Cancer Council's Beat Cancer project on behalf of its donors, the state Government through the Department of Health, and the Australian Government through the Medical Research Future Fund. T.E.H. is supported by an NBCF Fellowship (IIRS-19-009). M.G.L. and R.A.T. are supported by Fellowships from the Victorian Government through the Victorian Cancer Agency (MCRF18017 and MCRF15023). The research programs of L.M.B., L.A.S., and W.D.T. are supported by the Movember Foundation and the Prostate Cancer Foundation of Australia through Movember Revolutionary Team Awards. The authors thank the Australian Cancer Research Foundation (ACRF) Cancer Genomics Facility for assistance with Ago-HITS-CLIP and RNA-seq and the South Australian Health and Medical Research Institute (SAHMRI) Genomics Facility for assistance with ChIP-seq; Geraldine Laven-Law (University of Adelaide) for expert technical assistance; Nicholas Choo (Monash University), Birunthi Niranjan (Monash University), Roxanne Toivanen (Monash University), and Susan Woods (University of Adelaide) for expert technical assistance with organoid culture; Jindan Yu (Northwestern University) for providing a FOXA1 activity gene set; Peter Nelson and Ilsa Coleman (Fred Hutchinson Cancer Research Center) for providing transcriptomic data (Bluemn et al., 2017); and Emily Hackett-Jones (University of South Australia) for assistance with analysis of the Ago-HITS-CLIP data. We acknowledge the team that generated transcriptomic data from CRPC-Adeno and NEPC tumors (Beltran et al., 2016), which we obtained from dbGaP (accession number phs000909). The results published here are in part based on data generated by The Cancer Genome Atlas, established by the National Cancer Institute and the National Human Genome Research Institute, and we are grateful to the specimen donors and relevant research groups associated with this project. Finally, we thank the patients and clinicians who have generously supported the MURAL research platform.