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MicroRNA-135b Regulates ERα, AR and HIF1AN and Affects Breast and Prostate Cancer Cell Growth

Anna Aakula, Suvi-Katri Leivonen, Petteri Hintsanen, Tero Aittokallio, Yvonne Ceder, Anne-Lise Børresen-Dale, Merja Perälä, Päivi Östling, Olli Kallioniemi, MicroRNA-135b Regulates ERα, AR and HIF1AN and Affects Breast and Prostate Cancer Cell Growth. Molecular Oncology 9(7), 1287–1300, 2015.

http://dx.doi.org/10.1016/j.molonc.2015.03.001

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.

BibTeX entry:

@ARTICLE{jAaLeHiAiCeBxPeOKa15a,
  title = {MicroRNA-135b Regulates ERα, AR and HIF1AN and Affects Breast and Prostate Cancer Cell Growth},
  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},
  journal = {Molecular Oncology},
  volume = {9},
  number = {7},
  pages = {1287–1300},
  year = {2015},
  keywords = {MicroRNA (miRNA); Breast cancer (BCa); Prostate cancer (PCa); Estrogen receptor α (ERα); Androgen receptor (AR); Hypoxia inducible factor 1 alpha subunit inhibitor (HIF1AN)},
}

Belongs to TUCS Research Unit(s): Biomathematics Research Unit (BIOMATH)

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