A5030405138- MicroRNA in disease regulation
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- RNA Research and Splicing
- Prostate Cancer Treatment and Research
- Bladder and Urothelial Cancer Treatments
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Circular RNAs in diseases
- Molecular Biology Techniques and Applications
- Nanoparticles: synthesis and applications
- Metabolism, Diabetes, and Cancer
- Immune responses and vaccinations
- Diabetes and associated disorders
- Sirtuins and Resveratrol in Medicine
- Adipose Tissue and Metabolism
- Wnt/β-catenin signaling in development and cancer
- Pancreatic function and diabetes
- Immune Cell Function and Interaction
- interferon and immune responses
- RNA and protein synthesis mechanisms
- Cardiac Valve Diseases and Treatments
- Air Quality and Health Impacts
Aarhus University Hospital
2012-2025
Institute of Molecular Medicine
2017
Aarhus University
2012-2016
Tampere University Hospital
2014
Tampere University
2014
Heinrich Heine University Düsseldorf
2014
Düsseldorf University Hospital
2014
Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable resource for clinical research. However, nucleic acids extracted from FFPE fragmented and chemically modified making them challenging to use in molecular studies. We analysed 23 fresh-frozen (FF), 35 38 paired FF/FFPE specimens, representing six different human tissue types (bladder, prostate colon carcinoma; liver normal tissue; reactive tonsil) order examine the potential of samples next-generation sequencing (NGS) based...
Cancer cells secrete soluble factors and various extracellular vesicles, including exosomes, into their tissue microenvironment. The secretion of exosomes is speculated to facilitate local invasion metastatic spread. Here, we used an in vivo metastasis model human bladder carcinoma cell line T24 without capacity its two isogenic derivate lines SLT4 FL3, which form metastases the lungs liver mice, respectively. Cultivation CLAD1000 bioreactors rather than conventional culture flasks resulted...
In our study, whole-genome methylation arrays were applied to identify novel genes with tumor specific DNA of promoter CpG islands in pre-malignant and malignant colorectal lesions. Using a combination Illumina HumanMethylation27 beadchips, Methylation-Sensitive High Resolution Melting (MS-HRM) analysis, Exon (Affymetrix) the pattern ∼14,000 their transcript levels investigated six normal mucosas, adenomas 30 MSI MSS carcinomas. Sixty eight tumor-specific hypermethylation identified (p <...
OBJECTIVE Cytokines contribute to pancreatic β-cell death in type 1 diabetes. This effect is mediated by complex gene networks that remain be characterized. We presently utilized array analysis define the global expression pattern of genes, including spliced variants, modified cytokines interleukin (IL)-1β + interferon (IFN)-γ and tumor necrosis factor (TNF)-α IFN-γ primary rat β-cells. RESEARCH DESIGN AND METHODS Fluorescence-activated cell sorter–purified β-cells were exposed IL-1β or...
Bladder cancer (or urothelial cell carcinoma [UCC]) is characterized by field disease (malignant alterations in surrounding mucosa) and frequent recurrences. Whole-genome, exome, transcriptome sequencing of 38 tumors, including four metachronous tumor pairs 20 superficial identified an APOBEC mutational signature one-third. This was biased toward the sense strand, correlated with mean expression level, clustered near breakpoints. A>G mutations were up to eight times more on strand (p<0.002)...
Abstract An increasing body of evidence connects alterations in the process alternative splicing with cancer development and progression. However, a direct role factors as drivers is mostly unknown. We analysed gene copy number several colon lung tumours, found that encoding for factor SRSF6 amplified over‐expressed these cancers. Moreover, over‐expression immortal epithelial cells enhanced proliferation, protected them from chemotherapy‐induced cell death converted to be tumourigenic mice....
The toxic effects of silver nanoparticles (AgNPs) on cells are well established, but only limited studies the effect AgNPs and ions cellular transcriptome have been performed. In this study, gene expression in human lung epithelial cell line A549 exposed to 12.1 µg/ml (EC20) for 24 48h was compared with response control ion (Ag+) treated (1.3 µg/ml) using microarray analysis. Twenty-four hours AgNP altered regulation more than 1000 genes (more twofold regulation), whereas considerably fewer...
Objective "The obesity epidemic" has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease (NAFLD), for which effective treatments are demand. The polyphenol resveratrol prevents the development of experimental NAFLD through modulation cellular pathways involved calorie restriction. We aimed test hypothesis that alleviates a randomised, clinical trial. Materials and methods A total 28 overweight patients with transaminasemia histological were randomised...
The KIAA1199 transcript is upregulated in colon adenomas and downregulated upon β-catenin knockdown. Transcript profiling was performed on >500 biopsies, methylation data were compared with data. Immunohistochemistry assessed protein expression 270 stage II/III tumours (>3 years follow-up). effects of stable knockdown SW480 cells (three different constructs) studied using transcriptional profiling, proliferation analysis. strongly 95% adenocarcinomas. Absent normal mucosa correlated promotor...
Colorectal cancer (CRC) is one of the leading causes deaths in Western countries. A significant number CRC patients undergoing curatively intended surgery subsequently develop recurrence and die from disease. MicroRNAs (miRNAs) are aberrantly expressed cancers appear to have both diagnostic prognostic significance. In this study, we identified novel miRNAs associated with CRC, their possible mechanism action. TaqMan ® Human MicroRNA Array Set v2.0 was used profile expression 667 14 normal...
Background The polyphenol resveratrol has anti-inflammatory effects in various cells, tissues, animals and human settings of low-grade inflammation. Psoriasis is a disease both localized systemic Sirtuin1 enzyme thought to mediate the present skin known down regulate NF-κB; an important contributor development psoriasis. Consequently we investigated whether effect on Imiquimod induced psoriasis-like inflammation mice sought identify candidate genes, pathways interleukins mediating effects....
The kinase Mnk2 is a substrate of the MAPK pathway and phosphorylates translation initiation factor eIF4E. In humans, MKNK2, gene encoding for Mnk2, alternatively spliced yielding two splicing isoforms with differing last exons: Mnk2a, which contains MAPK-binding domain, Mnk2b, lacks it. We found that Mnk2a isoform downregulated in breast, lung, colon tumors tumor suppressive. directly interacts with, phosphorylates, activates, translocates p38α-MAPK into nucleus, leading to activation its...
Abstract Patients with short QT syndrome (SQTS) may present syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain <25% of cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene two unrelated families SQTS. The causes reduced surface expression AE3 and membrane bicarbonate transport. Slc4a3 knockdown zebrafish increased pH i , QTc, systolic duration, which is rescued by wildtype but...
The aim of this study was to identify deregulated transcription factors (TFs) in colorectal cancer (CRC) and evaluate their relation with the recurrence stage II CRC overall survival. Microarray-based transcript profiles 20 normal mucosas 424 samples were used 51 TFs displaying differential levels between mucosa CRC. For a subset these we provide vitro evidence that deregulation Wnt signalling pathway can lead alterations observed tissues. Furthermore, two independent cohorts...
Abstract Purpose: Available tools for prostate cancer diagnosis and prognosis are suboptimal novel biomarkers urgently needed. Here, we investigated the regulation biomarker potential of GABRE∼miR-452∼miR-224 genomic locus. Experimental Design: GABRE/miR-452/miR-224 transcriptional expression was quantified in 80 nonmalignant 281 tissue samples. promoter methylation determined by methylation-specific qPCR (MethyLight) 35 nonmalignant, 293 [radical prostatectomy (RP) cohort 1] 198 samples (RP...
Lipid metabolism is important for health and insulin action, yet the fundamental process of regulating lipid during muscle contraction incompletely understood. Here, we show that liver kinase B1 (LKB1) muscle-specific knockout (LKB1 MKO) mice display decreased fatty acid (FA) oxidation treadmill exercise. LKB1 MKO also SIK3 activity, increased histone deacetylase 4 expression, NAD+ concentration SIRT1 expression genes involved in FA oxidation. In AMP-activated protein (AMPK)α2 KO mice,...
The importance of AMPK in regulation fatty acid (FA) oxidation skeletal muscle with contraction/exercise is unresolved. Using a mouse model lacking both AMPKα1 and -α2 specifically (mdKO), we hypothesized that FA utilization would be impaired muscle. AMPKα mdKO mice displayed normal respiratory exchange ratio (RER) when fed chow or high-fat diet, prolonged fasting. However, vivo treadmill exercise at the same relative intensity induced higher RER compared to wild-type (WT = 0.81 ± 0.01...
Abstract This case-control study was designed to investigate the gene expression profile in skeletal muscle from severely insulin resistant patients with long-standing type 2 diabetes (T2D), and determine associated signaling pathways. Gene profiles were examined by whole transcriptome, strand-specific RNA-sequencing determined western blot. We identified 117 differentially expressed transcripts. Ingenuity Pathway Analysis related these differences abnormal morphology mitochondrial...
Alternative splicing is a crucial step in the generation of protein diversity and its misregulation observed many human cancer types. By analyzing 143 colorectal samples using exon arrays, SLC39A14, divalent cation transporter, was identified as being aberrantly spliced tumor samples. SLC39A14 contains two mutually exclusive exons 4A 4B 4A/4B ratio significantly altered adenomas (p = 3.6 × 10−10) cancers 9.4 10−11), independent microsatellite stability status. The findings were validated...
Gene silencing by DNA hypermethylation of CpG islands is a well-characterized phenomenon in cancer. The effect hypomethylation particular non-CpG island genes much less well described. By genome-wide screening, we identified 105 microsatellite stable (MSS) colorectal adenocarcinomas with an inverse correlation (Spearman's ρ ≤ -0.40) between methylation and expression. Of these, 35 (33%) were hypomethylated two them, APOLD1 = -0.82) SRPX2 -0.80) selected for further analyses. Hypomethylation...
Abstract Background Approximately half of all human genes use alternative transcription start sites (TSSs) to control mRNA levels and broaden the transcriptional output in healthy tissues. Aberrant expression patterns promoting carcinogenesis, however, may arise from promoter usage. Results By profiling 108 colorectal samples using exon arrays, we identified nine ( TCF12, OSBPL1A, TRAK1, ANK3, CHEK1, UGP2, LMO7, ACSL5 , SCIN ) showing tumor-specific TSS usage both adenoma cancer relative...
The gene Clusterin is a target for cancer therapy in clinical trials. indication intervention up-regulated expression. has been reported to be deregulated multiple types, including colorectal (CRC). However, CRC the studies have disagreed on whether up- or down-regulated by neoplastic cells. In present study we sought clarify expression and distribution of mRNAs proteins normal tissue through laser microdissection, variant-specific real time RT-PCR, immunohistochemistry, immunofluorescence,...