MicroRNA-135b regulates ERα, AR and HIF1AN and affects breast and prostate cancer cell growth.
Aakula, Anna ; Leivonen, Suvi-Katri ; Hintsanen, Petteri ; Aittokallio, Tero ; Ceder, Yvonne LU
; Børresen-Dale, Anne-Lise
; Perälä, Merja
; Östling, Päivi
and Kallioniemi, Olli
(2015)
In Molecular Oncology
9(7).
p.1287-1300
- Abstract
- MicroRNAs (miRNAs) regulate a wide range of cellular signaling pathways and biological processes in both physiological and pathological states such as cancer. We have previously identified miR-135b as a direct regulator of androgen receptor (AR) protein level in prostate cancer (PCa). We wanted to further explore the relationship of miR-135b to hormonal receptors, particularly estrogen receptor α (ERα). Here we show that miR-135b expression is lower in ERα-positive breast tumors as compared to ERα-negative samples in two independent breast cancer (BCa) patient cohorts (101 and 1302 samples). Additionally, the miR-135b expression is higher in AR-low PCa patient samples (47 samples). We identify ERα as a novel miR-135b target by... (More)
- MicroRNAs (miRNAs) regulate a wide range of cellular signaling pathways and biological processes in both physiological and pathological states such as cancer. We have previously identified miR-135b as a direct regulator of androgen receptor (AR) protein level in prostate cancer (PCa). We wanted to further explore the relationship of miR-135b to hormonal receptors, particularly estrogen receptor α (ERα). Here we show that miR-135b expression is lower in ERα-positive breast tumors as compared to ERα-negative samples in two independent breast cancer (BCa) patient cohorts (101 and 1302 samples). Additionally, the miR-135b expression is higher in AR-low PCa patient samples (47 samples). We identify ERα as a novel miR-135b target by demonstrating miR-135b binding to the 3'UTR of the ERα and decreased ERα protein and mRNA level upon miR-135b overexpression in BCa cells. MiR-135b reduces proliferation of ERα-positive BCa cells MCF-7 and BT-474 as well as AR-positive PCa cells LNCaP and 22Rv1 when grown in 2D. To identify other genes regulated by miR-135b we performed gene expression studies and found a link to the hypoxia inducible factor 1α (HIF1α) pathway. We show that miR-135b influences the protein level of the inhibitor for hypoxia inducible factor 1α (HIF1AN) and is able to bind to HIF1AN 3'UTR. Our study demonstrates that miR-135b regulates ERα, AR and HIF1AN protein levels through interaction with their 3'UTR regions, and proliferation in ERα-positive BCa and AR-positive PCa cells. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5340810
- author
- Aakula, Anna
; Leivonen, Suvi-Katri
; Hintsanen, Petteri
; Aittokallio, Tero
; Ceder, Yvonne
LU
; Børresen-Dale, Anne-Lise
; Perälä, Merja
; Östling, Päivi
and Kallioniemi, Olli
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Oncology
- volume
- 9
- issue
- 7
- pages
- 1287 - 1300
- publisher
- Elsevier
- external identifiers
-
- pmid:25907805
- wos:000359884800005
- scopus:84938198977
- pmid:25907805
- ISSN
- 1574-7891
- DOI
- 10.1016/j.molonc.2015.03.001
- language
- English
- LU publication?
- yes
- id
- 26df6d3c-509d-4477-a4e1-4501c1635eea (old id 5340810)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25907805?dopt=Abstract
- date added to LUP
- 2016-04-01 10:56:42
- date last changed
- 2022-04-12 19:08:55
@article{26df6d3c-509d-4477-a4e1-4501c1635eea,
abstract = {{MicroRNAs (miRNAs) regulate a wide range of cellular signaling pathways and biological processes in both physiological and pathological states such as cancer. We have previously identified miR-135b as a direct regulator of androgen receptor (AR) protein level in prostate cancer (PCa). We wanted to further explore the relationship of miR-135b to hormonal receptors, particularly estrogen receptor α (ERα). Here we show that miR-135b expression is lower in ERα-positive breast tumors as compared to ERα-negative samples in two independent breast cancer (BCa) patient cohorts (101 and 1302 samples). Additionally, the miR-135b expression is higher in AR-low PCa patient samples (47 samples). We identify ERα as a novel miR-135b target by demonstrating miR-135b binding to the 3'UTR of the ERα and decreased ERα protein and mRNA level upon miR-135b overexpression in BCa cells. MiR-135b reduces proliferation of ERα-positive BCa cells MCF-7 and BT-474 as well as AR-positive PCa cells LNCaP and 22Rv1 when grown in 2D. To identify other genes regulated by miR-135b we performed gene expression studies and found a link to the hypoxia inducible factor 1α (HIF1α) pathway. We show that miR-135b influences the protein level of the inhibitor for hypoxia inducible factor 1α (HIF1AN) and is able to bind to HIF1AN 3'UTR. Our study demonstrates that miR-135b regulates ERα, AR and HIF1AN protein levels through interaction with their 3'UTR regions, and proliferation in ERα-positive BCa and AR-positive PCa cells.}},
author = {{Aakula, Anna and Leivonen, Suvi-Katri and Hintsanen, Petteri and Aittokallio, Tero and Ceder, Yvonne and Børresen-Dale, Anne-Lise and Perälä, Merja and Östling, Päivi and Kallioniemi, Olli}},
issn = {{1574-7891}},
language = {{eng}},
number = {{7}},
pages = {{1287--1300}},
publisher = {{Elsevier}},
series = {{Molecular Oncology}},
title = {{MicroRNA-135b regulates ERα, AR and HIF1AN and affects breast and prostate cancer cell growth.}},
url = {{http://dx.doi.org/10.1016/j.molonc.2015.03.001}},
doi = {{10.1016/j.molonc.2015.03.001}},
volume = {{9}},
year = {{2015}},
}