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- Aakula, Anna, et al.
(författare)
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MicroRNA-135b regulates ERα, AR and HIF1AN and affects breast and prostate cancer cell growth.
- 2015
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 9:7, s. 1287-1300
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Tidskriftsartikel (refereegranskat)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.
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- Aaltonen, H. L., et al.
(författare)
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Deposition of inhaled nanoparticles is reduced in subjects with COPD and correlates with the extent of emphysema : Proof of concept for a novel diagnostic technique
- 2018
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 38:6, s. 1008-1014
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Tidskriftsartikel (refereegranskat)abstract
- Background: The diagnosis of chronic obstructive pulmonary disease (COPD) is often based on spirometry, which is not sensitive to early emphysema. We have recently described a method for assessing distal airspace dimensions by measuring recovery of nanoparticles in exhaled air after a single-breath inhalation followed by breath-hold. Recovery refers to the non-deposited particle fraction. The aim of this study was to explore differences in the recovery of exhaled nanoparticles in subjects with COPD and never-smoking controls. A secondary aim was to determine whether recovery correlates with the extent of emphysema. Method: A total of 19 patients with COPD and 19 controls underwent three repeats of single-breath nanoparticle inhalation followed by breath-hold. Particle concentrations in the inhaled aerosol, and in an alveolar sample exhaled after breath-hold, were measured to obtain recovery. Findings: The patients with COPD had a significantly higher mean recovery than controls, 0·128 ± 0·063 versus 0·074 ± 0·058; P = 0·010. Also, recovery correlated significantly with computed tomography (CT) densitometry variables (P<0·01) and diffusing capacity for carbon monoxide (DL,CO; P = 0·002). Interpretation: Higher recovery for emphysema patients, relative to controls, is explained by larger diffusion distances in enlarged distal airspaces. The nanoparticle inhalation method shows potential to be developed towards a tool to diagnose emphysema.
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