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miR-145 suppress the androgen receptor in prostate cancer cells and correlates to prostate cancer prognosis.

Larne, Olivia LU ; Hagman, Zandra LU ; Lilja, Hans LU ; Bjartell, Anders LU ; Edsjö, Anders LU and Ceder, Yvonne LU (2015) In Carcinogenesis 36(8). p.858-866
Abstract
Androgen signalling through the androgen receptor (AR) is essential for prostate cancer initiation, progression and transformation to the lethal castration-resistant state. The aim of this study was to characterize the mechanisms by which miR-145 deregulation contribute to prostate cancer progression. The miR-145 levels, measured by quantitative reverse transcription-polymerase chain reaction, were found to inversely correlate with occurrence of metastases, survival and androgen deprivation therapy response in a well-characterized prostate cancer cohort. Introduction of ectopic miR-145 in prostate cancer cells generated an inhibitory effect on the AR at both transcript and protein levels as well as its activity and downstream targets... (More)
Androgen signalling through the androgen receptor (AR) is essential for prostate cancer initiation, progression and transformation to the lethal castration-resistant state. The aim of this study was to characterize the mechanisms by which miR-145 deregulation contribute to prostate cancer progression. The miR-145 levels, measured by quantitative reverse transcription-polymerase chain reaction, were found to inversely correlate with occurrence of metastases, survival and androgen deprivation therapy response in a well-characterized prostate cancer cohort. Introduction of ectopic miR-145 in prostate cancer cells generated an inhibitory effect on the AR at both transcript and protein levels as well as its activity and downstream targets prostate-specific antigen (PSA), kallikrein-related peptidase 2 and TMPRSS2. The regulation was shown to be mediated by direct binding using Ago2-specific immunoprecipitation, but there was also indication of synergetic AR activation. These findings were verified in clinical prostate specimens by demonstrating inverse correlations between miR-145 and AR expression as well as serum PSA levels. In addition, miR-145 was found to regulate androgen-dependent cell growth in vitro. Our findings put forward novel possibilities of therapeutic intervention, as miR-145 potentially could decrease both the stem cells and the AR expressing bulk of the tumour and hence reduce the transformation to the deadly castration-resistant form of prostate cancer. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Carcinogenesis
volume
36
issue
8
pages
858 - 866
publisher
Oxford University Press
external identifiers
  • pmid:25969144
  • wos:000359314600006
  • scopus:84938687634
ISSN
0143-3334
DOI
10.1093/carcin/bgv063
language
English
LU publication?
yes
id
4998c306-f31d-4b9d-b5a0-3e1c3b2a3687 (old id 5453298)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25969144?dopt=Abstract
date added to LUP
2015-06-04 18:51:11
date last changed
2017-11-05 03:21:34
@article{4998c306-f31d-4b9d-b5a0-3e1c3b2a3687,
  abstract     = {Androgen signalling through the androgen receptor (AR) is essential for prostate cancer initiation, progression and transformation to the lethal castration-resistant state. The aim of this study was to characterize the mechanisms by which miR-145 deregulation contribute to prostate cancer progression. The miR-145 levels, measured by quantitative reverse transcription-polymerase chain reaction, were found to inversely correlate with occurrence of metastases, survival and androgen deprivation therapy response in a well-characterized prostate cancer cohort. Introduction of ectopic miR-145 in prostate cancer cells generated an inhibitory effect on the AR at both transcript and protein levels as well as its activity and downstream targets prostate-specific antigen (PSA), kallikrein-related peptidase 2 and TMPRSS2. The regulation was shown to be mediated by direct binding using Ago2-specific immunoprecipitation, but there was also indication of synergetic AR activation. These findings were verified in clinical prostate specimens by demonstrating inverse correlations between miR-145 and AR expression as well as serum PSA levels. In addition, miR-145 was found to regulate androgen-dependent cell growth in vitro. Our findings put forward novel possibilities of therapeutic intervention, as miR-145 potentially could decrease both the stem cells and the AR expressing bulk of the tumour and hence reduce the transformation to the deadly castration-resistant form of prostate cancer.},
  author       = {Larne, Olivia and Hagman, Zandra and Lilja, Hans and Bjartell, Anders and Edsjö, Anders and Ceder, Yvonne},
  issn         = {0143-3334},
  language     = {eng},
  number       = {8},
  pages        = {858--866},
  publisher    = {Oxford University Press},
  series       = {Carcinogenesis},
  title        = {miR-145 suppress the androgen receptor in prostate cancer cells and correlates to prostate cancer prognosis.},
  url          = {http://dx.doi.org/10.1093/carcin/bgv063},
  volume       = {36},
  year         = {2015},
}