MicroRNA-135b regulates ERa, AR and HIF1AN and affects breast and prostate cancer cell growth

Aakulaa Anna (Corresponding Author), Suvi-Katri Leivonen, Petteri Hintsanen, Tero Aittokallio, Yvonne Ceder, Anne-Lise Børresen-Dale, Merja Perälä, Päivi Östling, Olli Kallioniemi

Research output: Contribution to journalArticleScientificpeer-review

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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 a (ERa). Here we show that miR-135b expression is lower in ERa-positive breast tumors as compared to ERa-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 ERa as a novel miR-135b target by demonstrating miR-135b binding to the 3'UTR of the ERa and decreased ERa protein and mRNA level upon miR-135b overexpression in BCa cells. MiR-135b reduces proliferation of ERa-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 1a (HIF1a) pathway. We show that miR-135b influences the protein level of the inhibitor for hypoxia inducible factor 1a (HIF1AN) and is able to bind to HIF1AN 3'UTR. Our study demonstrates that miR-135b regulates ERa, AR and HIF1AN protein levels through interaction with their 3'UTR regions, and proliferation in ERa-positive BCa and AR-positive PCa cells.
Original languageEnglish
Pages (from-to)1287-1300
JournalMolecular Oncology
Volume9
Issue number7
DOIs
Publication statusPublished - 2015
MoE publication typeA1 Journal article-refereed

Fingerprint

Androgen Receptors
MicroRNAs
Estrogen Receptors
Prostatic Neoplasms
Breast Neoplasms
Growth
3' Untranslated Regions
Biological Phenomena
Proteins
MCF-7 Cells
Gene Expression
Messenger RNA
Genes

Keywords

  • MicroRNA (miRNA)
  • Breast cancer (BCa)
  • Prostate cancer (PCa)
  • Estrogen receptor a (ERa)
  • Androgen receptor (AR)
  • Hypoxia inducible factor 1 alpha subunit inhibitor (HIF1AN)

Cite this

Anna, A., Leivonen, S-K., Hintsanen, P., Aittokallio, T., Ceder, Y., Børresen-Dale, A-L., ... Kallioniemi, O. (2015). MicroRNA-135b regulates ERa, AR and HIF1AN and affects breast and prostate cancer cell growth. Molecular Oncology, 9(7), 1287-1300. https://doi.org/10.1016/j.molonc.2015.03.001
Anna, Aakulaa ; Leivonen, Suvi-Katri ; Hintsanen, Petteri ; Aittokallio, Tero ; Ceder, Yvonne ; Børresen-Dale, Anne-Lise ; Perälä, Merja ; Östling, Päivi ; Kallioniemi, Olli. / MicroRNA-135b regulates ERa, AR and HIF1AN and affects breast and prostate cancer cell growth. In: Molecular Oncology. 2015 ; Vol. 9, No. 7. pp. 1287-1300.
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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 a (ERa). Here we show that miR-135b expression is lower in ERa-positive breast tumors as compared to ERa-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 ERa as a novel miR-135b target by demonstrating miR-135b binding to the 3'UTR of the ERa and decreased ERa protein and mRNA level upon miR-135b overexpression in BCa cells. MiR-135b reduces proliferation of ERa-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 1a (HIF1a) pathway. We show that miR-135b influences the protein level of the inhibitor for hypoxia inducible factor 1a (HIF1AN) and is able to bind to HIF1AN 3'UTR. Our study demonstrates that miR-135b regulates ERa, AR and HIF1AN protein levels through interaction with their 3'UTR regions, and proliferation in ERa-positive BCa and AR-positive PCa cells.",
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Anna, A, Leivonen, S-K, Hintsanen, P, Aittokallio, T, Ceder, Y, Børresen-Dale, A-L, Perälä, M, Östling, P & Kallioniemi, O 2015, 'MicroRNA-135b regulates ERa, AR and HIF1AN and affects breast and prostate cancer cell growth', Molecular Oncology, vol. 9, no. 7, pp. 1287-1300. https://doi.org/10.1016/j.molonc.2015.03.001

MicroRNA-135b regulates ERa, AR and HIF1AN and affects breast and prostate cancer cell growth. / Anna, Aakulaa (Corresponding Author); Leivonen, Suvi-Katri; Hintsanen, Petteri; Aittokallio, Tero; Ceder, Yvonne; Børresen-Dale, Anne-Lise; Perälä, Merja; Östling, Päivi; Kallioniemi, Olli.

In: Molecular Oncology, Vol. 9, No. 7, 2015, p. 1287-1300.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - MicroRNA-135b regulates ERa, AR and HIF1AN and affects breast and prostate cancer cell growth

AU - Anna, Aakulaa

AU - Leivonen, Suvi-Katri

AU - Hintsanen, Petteri

AU - Aittokallio, Tero

AU - Ceder, Yvonne

AU - Børresen-Dale, Anne-Lise

AU - Perälä, Merja

AU - Östling, Päivi

AU - Kallioniemi, Olli

PY - 2015

Y1 - 2015

N2 - 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 a (ERa). Here we show that miR-135b expression is lower in ERa-positive breast tumors as compared to ERa-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 ERa as a novel miR-135b target by demonstrating miR-135b binding to the 3'UTR of the ERa and decreased ERa protein and mRNA level upon miR-135b overexpression in BCa cells. MiR-135b reduces proliferation of ERa-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 1a (HIF1a) pathway. We show that miR-135b influences the protein level of the inhibitor for hypoxia inducible factor 1a (HIF1AN) and is able to bind to HIF1AN 3'UTR. Our study demonstrates that miR-135b regulates ERa, AR and HIF1AN protein levels through interaction with their 3'UTR regions, and proliferation in ERa-positive BCa and AR-positive PCa cells.

AB - 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 a (ERa). Here we show that miR-135b expression is lower in ERa-positive breast tumors as compared to ERa-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 ERa as a novel miR-135b target by demonstrating miR-135b binding to the 3'UTR of the ERa and decreased ERa protein and mRNA level upon miR-135b overexpression in BCa cells. MiR-135b reduces proliferation of ERa-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 1a (HIF1a) pathway. We show that miR-135b influences the protein level of the inhibitor for hypoxia inducible factor 1a (HIF1AN) and is able to bind to HIF1AN 3'UTR. Our study demonstrates that miR-135b regulates ERa, AR and HIF1AN protein levels through interaction with their 3'UTR regions, and proliferation in ERa-positive BCa and AR-positive PCa cells.

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KW - Breast cancer (BCa)

KW - Prostate cancer (PCa)

KW - Estrogen receptor a (ERa)

KW - Androgen receptor (AR)

KW - Hypoxia inducible factor 1 alpha subunit inhibitor (HIF1AN)

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DO - 10.1016/j.molonc.2015.03.001

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EP - 1300

JO - Molecular Oncology

JF - Molecular Oncology

SN - 1574-7891

IS - 7

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Anna A, Leivonen S-K, Hintsanen P, Aittokallio T, Ceder Y, Børresen-Dale A-L et al. MicroRNA-135b regulates ERa, AR and HIF1AN and affects breast and prostate cancer cell growth. Molecular Oncology. 2015;9(7):1287-1300. https://doi.org/10.1016/j.molonc.2015.03.001