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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5453298
- author
- Larne, Olivia
LU
; Hagman, Zandra
LU
; Lilja, Hans
LU
; Bjartell, Anders
LU
; Edsjö, Anders
LU
and Ceder, Yvonne
LU
- organization
- publishing date
- 2015
- 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
- pmid:25969144
- 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
- 2016-04-01 10:57:08
- date last changed
- 2022-05-19 02:19:59
@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 = {{https://lup.lub.lu.se/search/files/2263093/8571920.pdf}},
doi = {{10.1093/carcin/bgv063}},
volume = {{36}},
year = {{2015}},
}