A5072920250- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Nail Diseases and Treatments
- Skin and Cellular Biology Research
- Cancer Genomics and Diagnostics
- Silk-based biomaterials and applications
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Gastrointestinal Tumor Research and Treatment
- Cancer, Lipids, and Metabolism
- Prostate Cancer Treatment and Research
- Renal Transplantation Outcomes and Treatments
- Metabolism and Genetic Disorders
- Genetics and Neurodevelopmental Disorders
- Estrogen and related hormone effects
- Eicosanoids and Hypertension Pharmacology
- Molecular Biology Techniques and Applications
- Mycobacterium research and diagnosis
- Folate and B Vitamins Research
- Inflammatory mediators and NSAID effects
- Gut microbiota and health
- Circular RNAs in diseases
- Cancer, Hypoxia, and Metabolism
University of Augsburg
2024
German Cancer Research Center
1987-2020
Heidelberg University
1987-2020
University Hospital Heidelberg
2012-2018
Georg Speyer Haus
2012
Cold Spring Harbor Laboratory
2012
Ionis Pharmaceuticals (United States)
2012
Helmholtz Institute for RNA-based Infection Research
2012
Abstract The long noncoding RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), also known as MALAT-1 or NEAT2 (nuclear-enriched abundant 2), is a highly conserved nuclear (ncRNA) and predictive marker for metastasis development in cancer. To uncover its functional importance, we developed knockout model human tumor cells by genomically integrating destabilizing elements using zinc finger nucleases. achieved 1,000-fold silencing provides unique loss-of-function model....
The metastasis-associated lung adenocarcinoma transcript 1, MALAT1, is a long non-coding RNA (lncRNA) that has been discovered as marker for cancer metastasis. It highly abundant, its expression strongly regulated in many tumor entities including and hepatocellular carcinoma well physiological processes, it associated with binding proteins conserved throughout evolution. nuclear MALAT-1 functionally gene regulation alternative splicing shown to impact proliferation, apoptosis, migration...
Selected long noncoding RNAs (lncRNAs) have been shown to play important roles in carcinogenesis. Although the cellular functions of these transcripts can be diverse, many lncRNAs regulate gene expression. In contrast, factors that control expression remain largely unknown. Here we investigated impact RNA binding proteins on liver cancer-associated lncRNA HULC (highly up-regulated cancer). First, validated strong up-regulation human hepatocellular carcinoma. To elucidate posttranscriptional...
The CRISPR/Cas9 system provides a revolutionary genome editing tool for all areas of molecular biology. In long non-coding RNA (lncRNA) research, the Cas9 nuclease can delete lncRNA genes or introduce RNA-destabilizing elements into their locus. nuclease-deficient dCas9 mutant retains its RNA-dependent DNA-binding activity and modulate gene expression when fused to transcriptional repressor activator domains. Here, we systematically analyze whether CRISPR approaches are suitable target...
Synonymous mutations have been viewed as silent mutations, since they only affect the DNA and mRNA, but not amino acid sequence of resulting protein. Nonetheless, recent studies suggest their significant impact on splicing, RNA stability, folding, translation or co-translational protein folding. Hence, we compile 659194 synonymous found in human cancer characterize properties. We provide user-friendly, comprehensive resource for cancer, SynMICdb ( http://SynMICdb.dkfz.de ), which also...
Significance Long noncoding RNAs (lncRNAs) are starting to be recognized as critical molecules for cellular transformation, although only a few candidates have so far been characterized. Here we report that TP53TG1 is an lncRNA the correct response of p53 DNA damage. The cancer growth suppressor features linked its ability block tumorigenic activity RNA binding protein YBX1. methylation-associated silencing produces aggressive tumors resistant death when DNA-damaging agents and small...
The identification of viability-associated long noncoding RNAs (lncRNAs) might be a promising rationale for new therapeutic approaches in liver cancer. Here, we applied an RNA interference screening approach hepatocellular carcinoma (HCC) cell lines to find lncRNAs. Among the multiple identified lncRNAs with significant impact on HCC viability, selected cancer susceptibility 9 (CASC9) due strength its phenotype, expression, and up-regulation versus normal liver. CASC9 regulated viability...
Abstract Long intergenic non-coding RNA- Nucleotide Metabolism Regulator (lincNMR ) is a long RNA (lncRNA) which induced in hepatocellular carcinoma. Its depletion invokes proliferation defect, triggers senescence and inhibits colony formation liver, but also breast lung cancer cells. Triple-label SILAC proteomics profiles reveal deregulation of key cell cycle regulators lincNMR -depleted cells like the dNTP synthesizing enzymes RRM2, TYMS TK1, implicating regulating nucleotide metabolism....
When applied to NMRI mouse skin in vivo, phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and 12-O-retinoylphorbol-13-acetate (RPA) have been found induce two early waves of prostaglandin E2 (PGE2) synthesis after 15 90 min a delayed accumulation F2 alpha (PGF2 alpha) 2 h. With respect PGF2 formation different activities both agents were observed, that TPA but not RPA induced additional 4 17 Functionally, PGE2 was previously shown be an endogenous mediator the TPA- or...
Long non-coding RNAs (lncRNAs) have been proven to play important roles in diverse cellular processes including the DNA damage response. Nearly 40% of annotated lncRNAs are transcribed antisense direction other genes and often implicated their regulation via transcript- or transcription-dependent mechanisms. However, it remains unclear whether inverse correlation gene expression would generally point toward a regulatory interaction between genes. Here, we profiled lncRNA mRNA lung liver...
Abstract Background Recently, we introduced Stroma-AReactive-Invasion-Front-Areas (SARIFA) as a novel hematoxylin–eosin (H&E)-based histopathologic prognostic biomarker for various gastrointestinal cancers, closely related to lipid metabolism. To date, no studies on SARIFA, which is defined direct tumor-adipocyte-interaction, beyond the alimentary tract exist. Hence, objective of our current investigation was study significance SARIFA in pT3a prostate cancer (PCa) and explore its...
In recent years, long non-coding RNA (lncRNA) research has identified essential roles of these transcripts in virtually all physiological cellular processes including tumorigenesis, but their functions and molecular mechanisms are poorly understood. this study, we performed a high-throughput siRNA screen targeting 638 lncRNAs deregulated cancer entities to analyse impact on cell division by using time-lapse microscopy. We 26 affecting morphology cycle LINC00152. This transcript was...
Using discontinuous Percoll density gradient centrifugation, keratinocytes from neonatal mouse skin were separated into four fractions. The fractions characterized by light microscopy, indirect immunofluorescence using lectins (Bandeira simplicifolia and Ulex europaeus) or an antibody against bullous pemphigoid antigen, electrophoretic analysis of the keratin polypeptide patterns. Two fractions, F1 F2, identified as being derived suprabasal layers two F3 F4, originating basal cell layer. F4...
Aberrant expression of noncoding RNAs plays a critical role during tumorigenesis. To uncover novel functions long non-coding RNA (lncRNA) in lung adenocarcinoma, we used microarray-based screen identifying LINC00673 with elevated matched tumor versus normal tissue. We report that loss is sufficient to trigger cellular senescence, suppressive mechanism associated permanent cell cycle arrest, both cancer and cells p53-dependent manner. LINC00673-depleted fail efficiently transit from G1-...
Abstract A major challenge in kidney transplantation (KT) is the large interpatient variability pharmacokinetics of immunosuppressive drugs. Here, we explored role gut microbiome interindividual variation drug metabolism. Analysis 38 fecal communities, including 10 from KT recipients, and 45 bacterial species against 25 drugs, revealed significant drug-specific differences Notably, 15 16 immunosuppressants tested were metabolized by at least one microbial community, found specific species,...
Abstract The long non-coding RNA MALAT1 was one of the first lncRNAs associated with cancer: it is a highly conserved nuclear ncRNA and predictive marker for metastasis development in lung cancer. However, its high abundance localization have greatly hampered functional analysis since only inefficiently knocked down by interference (RNAi). To uncover importance, we developed knockout model human tumor cells genomically integrating destabilizing elements site-specifically into locus using...
Abstract The highly conserved long non-coding RNA MALAT-1 (Metastasis-Associated in Lung Adenocarcinoma Transcript 1) had been discovered as a prognostic marker associated with poor survival and development of distant metastasis lung adenocarcinoma. Since then, it has found to be deregulated numerous tumor entities linked splicing. However, its functional relevance cells remains elucidated. Knockdown models for MALAT1 have described but suffer from insufficient silencing efficiency the...