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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)
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author
organization
publishing date
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
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
2015-05-02 12:56:25
date last changed
2017-11-12 03:13:59
@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},
  volume       = {9},
  year         = {2015},
}