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Upregulation of miR-96 Enhances Cellular Proliferation of Prostate Cancer Cells through FOXO1.

Haflidadottir, Benedikta LU ; Larne, Olivia LU ; Martin, Myriam LU ; Persson, Margareta LU ; Edsjö, Anders LU ; Bjartell, Anders LU and Ceder, Yvonne LU orcid (2013) In PLoS ONE 8(8).
Abstract
Aberrant expression of miR-96 in prostate cancer has previously been reported. However, the role and mechanism of action of miR-96 in prostate cancer has not been determined. In this study, the diagnostic and prognostic properties of miR-96 expression levels were investigated by qRT-PCR in two well documented prostate cancer cohorts. The miR-96 expression was found to be significantly higher in prostate cancer patients and correlate with WHO grade, and decreased overall survival time; patients with low levels of miR-96 lived 1.5 years longer than patients with high miR-96 levels. The therapeutic potential was further investigated in vitro, showing that ectopic levels of miR-96 enhances growth and cellular proliferation in prostate cancer... (More)
Aberrant expression of miR-96 in prostate cancer has previously been reported. However, the role and mechanism of action of miR-96 in prostate cancer has not been determined. In this study, the diagnostic and prognostic properties of miR-96 expression levels were investigated by qRT-PCR in two well documented prostate cancer cohorts. The miR-96 expression was found to be significantly higher in prostate cancer patients and correlate with WHO grade, and decreased overall survival time; patients with low levels of miR-96 lived 1.5 years longer than patients with high miR-96 levels. The therapeutic potential was further investigated in vitro, showing that ectopic levels of miR-96 enhances growth and cellular proliferation in prostate cancer cells, implying that miR-96 has oncogenic properties in this setting. We demonstrate that miR-96 expression decreases the transcript and protein levels of FOXO1 by binding to one of two predicted binding sites in the FOXO1 3'UTR sequence. Blocking this binding site completely inhibited the growth enhancement conveyed by miR-96. This finding was corroborated in a large external prostate cancer patient cohort where miR-96 expression inversely correlated to FOXO1 expression. Taken together these findings indicate that miR-96 plays a key role in prostate cancer cellular proliferation and can enhance prostate cancer progression. This knowledge might be utilized for the development of novel therapeutic tools for prostate cancer. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
8
issue
8
article number
e72400
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000323097300197
  • pmid:23951320
  • scopus:84881538006
  • pmid:23951320
ISSN
1932-6203
DOI
10.1371/journal.pone.0072400
language
English
LU publication?
yes
id
abef0d0f-288d-4371-8220-eaa7a599cf18 (old id 4005580)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23951320?dopt=Abstract
date added to LUP
2016-04-01 14:24:44
date last changed
2022-05-19 02:20:01
@article{abef0d0f-288d-4371-8220-eaa7a599cf18,
  abstract     = {{Aberrant expression of miR-96 in prostate cancer has previously been reported. However, the role and mechanism of action of miR-96 in prostate cancer has not been determined. In this study, the diagnostic and prognostic properties of miR-96 expression levels were investigated by qRT-PCR in two well documented prostate cancer cohorts. The miR-96 expression was found to be significantly higher in prostate cancer patients and correlate with WHO grade, and decreased overall survival time; patients with low levels of miR-96 lived 1.5 years longer than patients with high miR-96 levels. The therapeutic potential was further investigated in vitro, showing that ectopic levels of miR-96 enhances growth and cellular proliferation in prostate cancer cells, implying that miR-96 has oncogenic properties in this setting. We demonstrate that miR-96 expression decreases the transcript and protein levels of FOXO1 by binding to one of two predicted binding sites in the FOXO1 3'UTR sequence. Blocking this binding site completely inhibited the growth enhancement conveyed by miR-96. This finding was corroborated in a large external prostate cancer patient cohort where miR-96 expression inversely correlated to FOXO1 expression. Taken together these findings indicate that miR-96 plays a key role in prostate cancer cellular proliferation and can enhance prostate cancer progression. This knowledge might be utilized for the development of novel therapeutic tools for prostate cancer.}},
  author       = {{Haflidadottir, Benedikta and Larne, Olivia and Martin, Myriam and Persson, Margareta and Edsjö, Anders and Bjartell, Anders and Ceder, Yvonne}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{8}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Upregulation of miR-96 Enhances Cellular Proliferation of Prostate Cancer Cells through FOXO1.}},
  url          = {{https://lup.lub.lu.se/search/files/3962308/4300678.pdf}},
  doi          = {{10.1371/journal.pone.0072400}},
  volume       = {{8}},
  year         = {{2013}},
}