Interplay between steroid signalling and microRNAs: implications for hormone-dependent cancers

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Title: Interplay between steroid signalling and microRNAs: implications for hormone-dependent cancers
Author(s): Fletcher, CE
Dart, DA
Bevan, CL
Item Type: Journal Article
Abstract: Hormones are key drivers of cancer development. To date, interest has largely been focussed on the classical model of hormonal gene regulation, but there is increasing evidence for a role of hormone signalling pathways in post-translational regulation of gene expression. In particular, a complex and dynamic network of bi-directional interactions with microRNAs (miRs) at all stages of biogenesis and during target gene repression is emerging. miRs, which act mainly by negatively regulating gene expression through association with 3′-UTRs of mRNA species, are increasingly understood to be important in development, normal physiology and pathogenesis. Given recent demonstrations of altered miR profiles in a diverse range of cancers, their ability to function as oncogenes or tumour suppressors, and hormonal regulation of miRs, understanding mechanisms by which miRs are generated and regulated is vitally important. miRs are transcribed by RNA polymerase II and then processed in the nucleus by the Drosha-containing Microprocessor complex and in the cytoplasm by Dicer, before mature miRs are incorporated into the RNA-induced silencing complex. It is increasingly evident that multiple cellular signalling pathways converge upon the miR biogenesis cascade, adding further layers of regulatory complexity to modulate miR maturation. This review summarises recent advances in identification of novel components and regulators of the Microprocessor and Dicer complexes, with particular emphasis on the role of hormone signalling pathways in regulating their activity. Understanding hormone regulation of miR production and how this is perturbed in cancer are critical for the development of miR-based therapeutics and biomarkers.
Publication Date: 25-Jul-2014
Date of Acceptance: 24-Jul-2014
URI: http://hdl.handle.net/10044/1/43894
DOI: http://dx.doi.org/10.1530/ERC-14-0208
ISSN: 1479-6821
Publisher: BioScientifica
Start Page: R409
End Page: R429
Journal / Book Title: Endocrine-Related Cancer
Volume: 21
Issue: 5
Copyright Statement: © 2014 Society for Endocrinology. This is not the definitive version of record of this article.This manuscript has been accepted for publication in Endocrine-Related Cancer, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at http://dx.doi.org/10.1530/ERC-14-0208
Sponsor/Funder: Cancer Research UK
Prostate Cancer UK
Rosetrees Trust
Wellcome Trust
Funder's Grant Number: C37990/A12196
PG10-25
JS16/M192
097816/Z/11/A
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Endocrinology & Metabolism
microRNA
prostate
breast
androgen
estrogen
Drosha
microprocessor
Dicer
ESTROGEN-RECEPTOR-ALPHA
INDEPENDENT PROSTATE-CANCER
INDUCED SILENCING COMPLEX
RNA-BINDING PROTEIN
HUMAN BREAST-CANCER
ANDROGEN RECEPTOR
MESSENGER-RNA
GENE-EXPRESSION
CELL-LINES
CAENORHABDITIS-ELEGANS
Dicer
Drosha
androgen
breast
estrogen
microRNA
microprocessor
prostate
Animals
Estrogen Receptor alpha
Hormones
Humans
MicroRNAs
Neoplasms, Hormone-Dependent
Receptors, Androgen
Signal Transduction
Steroids
Animals
Humans
Neoplasms, Hormone-Dependent
Steroids
Hormones
Receptors, Androgen
Estrogen Receptor alpha
MicroRNAs
Signal Transduction
Oncology & Carcinogenesis
11 Medical And Health Sciences
06 Biological Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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