A5058151791- RNA modifications and cancer
- RNA Research and Splicing
- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- Virus-based gene therapy research
- MicroRNA in disease regulation
- Cell Image Analysis Techniques
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Thyroid Cancer Diagnosis and Treatment
- Image Processing Techniques and Applications
- Plant Disease Resistance and Genetics
- SARS-CoV-2 and COVID-19 Research
- Digital Imaging for Blood Diseases
- Cancer Mechanisms and Therapy
- Medical Image Segmentation Techniques
- Acute Myeloid Leukemia Research
- Lung Cancer Research Studies
- Neuroendocrine Tumor Research Advances
- Extracellular vesicles in disease
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- SARS-CoV-2 detection and testing
- Calpain Protease Function and Regulation
Martin Luther University Halle-Wittenberg
2014-2025
Institute of Molecular Medicine
2019-2025
Luther University
2023
The oncofetal IGF2 mRNA binding proteins (IGF2BPs) are upregulated in most cancers but their paralogue-specific roles tumor cells remain poorly understood. In a panel of five cancer-derived cell lines, IGF2BP1 shows highly conserved oncogenic potential. Consistently, the deletion impairs growth and metastasis ovarian nude mice. Gene expression analyses reveal that knockdown IGF2BPs is associated with downregulation mRNAs prone to miRNA regulation. All three preferentially associate upstream...
The tumor-suppressive let-7 microRNA family targets various oncogene-encoding mRNAs. We identify the HMGA2, LIN28B and IGF2BP1 to form a antagonizing self-promoting oncogenic triangle. Surprisingly, 3′-end processing of mRNAs is unaltered in aggressive cancers tumor-derived cells although synthesis was proposed escape attack by APA-dependent (alternative polyadenylation) 3′ UTR shortening. However, expression triangle factors inversely correlated with levels promoted impairing biogenesis....
Abstract Background Neuroblastoma is the most common solid tumor in infants accounting for approximately 15% of all cancer-related deaths. Over 50% high-risk neuroblastoma relapse, emphasizing need novel drug targets and therapeutic strategies. In neuroblastoma, chromosomal gains at chromosome 17q, including IGF2BP1 , MYCN amplification 2p are associated with adverse outcome. Recent, pre-clinical evidence indicates feasibility direct indirect targeting cancer treatment. Methods Candidate...
Abstract Non-small cell lung cancer (NSCLC) is the leading cause of death worldwide underlining urgent need for new biomarkers and therapeutic targets this disease. Long noncoding RNAs are critical players in NSCLC but role small RNA species not well understood. In present study, we investigated H/ACA box nucleolar (snoRNAs) snoRNA-bound ribonucleoproteins (snoRNPs) tumorigenesis NSCLC. snoRNPs including NOP10 core protein were highly expressed High levels either mRNA or associated with poor...
The oncofetal IGF2 mRNA-binding protein 1 (IGF2BP1) promotes tumor progression in a variety of solid tumors and its expression is associated with adverse prognosis. main role proposed for IGF2BP1 cancer cells the stabilization mRNAs encoding pro-oncogenic factors. Several IGF2BP1-RNA association studies, however, revealed plethora putative targets. Thus, at present conserved target RNAs pathways controlled by remain elusive. In this study, we set genes hallmark showing pattern deregulation...
Abstract The Hippo/YAP1 signaling pathway regulates normal development by controlling contact inhibition of growth. In cancer, YAP1 activation is often dysregulated, leading to excessive tumor growth and metastasis. SRC kinase can cross talk Hippo disrupting adherens junctions, repressing the cascade, or activating promote proliferation. Here, we demonstrate that IGF2 messenger RNA-binding protein 1 (IGF2BP1) impedes repression in carcinomas. IGF2BP1 stabilizes RNA (mRNA) enhances synthesis...
MicroRNAs (miRNAs) control gene expression at the post-transcriptional level. However, identification of miRNAs regulating fate a specific messenger RNA remains limited due to imperfect complementarity and targeted transcripts. Here, we describe miTRAP (miRNA trapping by in vitro affinity purification), an advanced protocol previously reported MS2-tethering approaches. MiTRAP allows rapid targeting transcribed cell lysates. Selective co-purification regulatory was confirmed for MYC- as well...
Anaplastic thyroid carcinomas (ATC) are rare, but represent the most lethal malignancy of thyroid. Selective molecular markers and drivers distinguishing ATC from other follicular origin remain largely unknown, limiting advances in diagnosis treatment. In a retrospective study, we analyzed gene expression 36 ATC, 18 poorly differentiated, 132 papillary, 55 carcinoma, as well 124 paired unpaired normal tissues three independent cohorts by RNA-sequencing immunohistochemistry. data test cohort...
Epithelial-to-mesenchymal transition (EMT) is a hallmark of aggressive, mesenchymal-like high-grade serous ovarian carcinoma (HGSOC). The SRC kinase key driver cancer-associated EMT promoting adherens junction (AJ) disassembly by phosphorylation-driven internalization and degradation AJ proteins. Here, we show that the IGF2 mRNA-binding protein 1 (IGF2BP1) up-regulated in HGSOC promotes activation previously unknown protein-ligand-induced, but RNA-independent mechanism. IGF2BP1-driven...
Abstract Background Cancer metastases are the main cause of lethality. The five-year survival rate for patients diagnosed with advanced stage oral cancer is 30%. Hence, identification novel therapeutic targets an urgent need. However, tumors comprised a heterogeneous collection cells distinct genetic and molecular profiles that can differentially promote metastasis making therapy development challenging task. Here, we leveraged intratumoral heterogeneity in order to identify drivers cell...
MiToBo is a toolbox and Java library for solving basic as well advanced image processing analysis tasks. It features rich collection of fundamental, intermediate high-level operators algorithms couple sophisticated tools specific biological biomedical applications. These include elucidating cellular morphology locomotion the characterization certain intracellular particles structures.MiToBo builds upon integrates into widely-used software packages ImageJ Fiji [11, 10], all its can easily be...
Abstract The differentiation and regeneration of skeletal muscle from myoblasts to myotubes involves myogenic transcription factors, such as myocardin-related factor A (MRTF-A) serum response (SRF). In addition, post-transcriptional regulation by miRNAs is required during myogenesis. Here, we provide evidence for novel mechanisms regulating MRTF-A differentiation. Endogenous protein abundance activity decreased C2C12 differentiation, which was attributable miRNA-directed inhibition....
MYCN gene amplification and upregulated expression are major hallmarks in the progression of high-risk neuroblastoma. function modulating synthesis neuroblastoma is controlled at virtually every level, including poorly understood regulation post-transcriptional level. modulates various microRNAs miR-17-92 cluster. mRNA itself subjected to control by miRNAs, most prominently cluster that balances feed-back regulation. This homeostasis seems disturbed where upregulation coincides with severely...
MicroRNAs (miRs) contribute to different aspects of cardiovascular pathology, among others cardiac hypertrophy and atrial fibrillation. The aim our study was evaluate the impact miR-221/222 on electrical remodeling. Cardiac miR expression analyzed in a mouse model with altered electrocardiography parameters severe heart hypertrophy. Next generation sequencing revealed 14 differentially expressed miRs hypertrophic hearts, miR-221 -222 being strongest regulated miR-cluster. This increase...
Collecting duct carcinoma (CDC) is a rare renal cell subtype with very poor prognosis. There have been only few studies on gene expression analysis in CDCs. We compared the profiles of two CDC cases those eight normal tissues patients. At threshold |log2fold-change| ≥ 1, 3349 genes were upregulated and 1947 downregulated CDCs to samples. Pathway deregulated revealed that cancer pathways cycle most prominent The was keratin 17, cubilin. Among four solute carrier (SLC3A1, SLC9A3, SLC26A7,...
Atherosclerosis underlies the majority of cardiovascular events, consequent to non-resolving inflammation. Considerable evidence implicates autophagy dysfunction at core this inflammatory condition, but basis is not fully understood.Using an in vitro model lipid-laden macrophages, activity-based probes and high-throughput techniques, we studied role cysteine proteases cathepsins autophagy.We showed that cathepsin activity suppressed by oxidized lipids has indispensable autophagy-lysosomal...
Neuroblastoma is a common childhood cancer with almost third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have reported roles in neuroblastoma development patient outcome, the role RBPs relatively unstudied. In order elucidate novel involved MYCN-amplified high-risk subtypes, we performed...
Neuroendocrine neoplasms (NENs) represent a heterogenous class of highly vascularized that are increasing in prevalence and predominantly diagnosed at metastatic state. The molecular mechanisms leading to tumor initiation, metastasis, chemoresistance still under investigation. Hence, identification novel therapeutic targets is great interest. Here, we demonstrate the RNA-binding Protein IGF2BP1 post-transcriptional regulator components Polycomb repressive complex 2 (PRC2), an epigenic...
The different steps of gene expression are intimately linked to coordinate and regulate this complex process. During transcription, numerous RNA-binding proteins already loaded onto the nascent mRNA package into a messenger ribonucleoprotein particle (mRNP). These often also involved in other than packaging. For example, TREX functions mRNP packaging nuclear export. Previously, we showed that Prp19 splicing (Prp19C) is needed for efficient transcription as well occupancy at transcribed...
The function of complex networks in the nervous system relies on proper formation neuronal contacts and their remodeling. To decipher molecular mechanisms underlying these processes, it is essential to establish unbiased automated tools allowing correlation neurite morphology subcellular distribution molecules by quantitative means. We developed NeuronAnalyzer2D, a plugin for ImageJ, which allows extraction cell morphologies from two dimensional high resolution images, particular with...
Anaplastic thyroid carcinoma (ATC) is the most fatal and rapidly evolving endocrine malignancy invading head neck region accounts for up to 50% of cancer-associated deaths. Deregulation microRNA (miRNA) expression promotes progression by modulating reorganization ATC transcriptome. Here, we applied comparative miRNA-mRNA sequencing on a cohort 28 carcinomas unravel association deregulated miRNA mRNA expression. This identified 85 miRNAs significantly in ATC. By establishing new analysis...
MicroRNAs (miRs) contribute to different aspects of cardiovascular pathology, among them cardiac hypertrophy and atrial fibrillation. Cardiac miR expression was analyzed in a mouse model with structural electrical remodeling. Next-generation sequencing revealed that miR-208b-3p ~25-fold upregulated. Therefore, the aim our study evaluate impact miR-208b on protein expression. First, an undirected approach comparing whole RNA data miR-walk 2.0 3'-UTR targets 58 potential being regulated. We...
Abstract Epithelial-to-mesenchymal transition (EMT) is a hallmark of aggressive, mesenchymal-like high-grade serous ovarian carcinoma (HG-SOC). The SRC kinase key driver cancer-associated EMT promoting adherens junction (AJ) disassembly by phosphorylation-driven internalization and degradation AJ proteins. Here we show, that the IGF2 mRNA binding protein 1 (IGF2BP1) up-regulated in HG-SOC promotes activation previously unknown protein-ligand-induced, but RNA-independent mechanism....
Renowned as the predominant form of kidney cancer, clear cell renal carcinoma (ccRCC) exhibits susceptibility to immunotherapies due its specific expression profile well notable immune infiltration. Despite this, effectively treating metastatic ccRCC remains a significant challenge, necessitating more profound comprehension underlying molecular mechanisms governing progression. Here, we unveil that enhanced RNA-binding protein DNA dC → dU-editing enzyme APOBEC-3C (APOBEC3C; also known A3C)...