A5012658184- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- Chronic Lymphocytic Leukemia Research
- Phagocytosis and Immune Regulation
- RNA Research and Splicing
- Cell Image Analysis Techniques
- Immune Cell Function and Interaction
- Cancer-related gene regulation
- Wnt/β-catenin signaling in development and cancer
- MicroRNA in disease regulation
- Skin and Cellular Biology Research
- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Renal and related cancers
- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- Adipokines, Inflammation, and Metabolic Diseases
- Hippo pathway signaling and YAP/TAZ
- Medical Image Segmentation Techniques
- Cellular Mechanics and Interactions
- Cancer Cells and Metastasis
- Advanced biosensing and bioanalysis techniques
- Neurotransmitter Receptor Influence on Behavior
- Galectins and Cancer Biology
Martin Luther University Halle-Wittenberg
2013-2025
Institute of Molecular Medicine
2020-2025
Haverford College
2019
The oncofetal mRNA-binding protein IGF2BP1 and the transcriptional regulator SRF modulate gene expression in cancer. In cancer cells, we demonstrate that promotes of a conserved N6-methyladenosine (m6A)-dependent manner by impairing miRNA-directed decay mRNA. This results enhanced SRF-dependent activity tumor cell growth invasion. At post-transcriptional level, sustains various SRF-target genes. majority these SRF/IGF2BP1-enhanced genes, including PDLIM7 FOXK1, show upregulation with...
In primary neurons, the oncofetal RNA-binding protein IGF2BP1 (IGF2 mRNA-binding 1) controls spatially restricted β-actin (ACTB) mRNA translation and modulates growth cone guidance. cultured tumor-derived cells, was shown to regulate formation of lamellipodia invadopodia. However, how via which target mRNAs motility cells has remained elusive. this study, we reveal that promotes velocity directionality cell migration by determining cytoplasmic fate two novel mRNAs: MAPK4 PTEN. Inhibition...
The IGF2 mRNA-binding protein 1 (IGF2BP1) is a non-catalytic post-transcriptional enhancer of tumor growth upregulated and associated with adverse prognosis in solid cancers. However, conserved effector pathway(s) the feasibility targeting IGF2BP1 cancer remained elusive. We reveal that E2F-driven hallmark promotes G1/S cell cycle transition by stabilizing mRNAs encoding positive regulators this checkpoint like E2F1. This IGF2BP1-driven shortening G1 phase relies on 3'UTR-, miRNA-...
During cellular stress, protein synthesis is severely reduced and bulk mRNA recruited to stress granules (SGs). Previously, we showed that the SG-recruited IGF2 mRNA-binding 1 (IGF2BP1) interferes with target degradation during stress. Whether this requires formation of SGs remained elusive. Here, demonstrate sustained inhibition visible concomitant knockdown TIA1, TIAR G3BP1. FRAP photo-conversion studies, however, indicate these proteins only transiently associate SGs. This suggests...
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....
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 Gain of chromosome 21 (Hsa21) is among the most frequent aneuploidies in leukemia. However, it remains unclear how partial or complete amplifications Hsa21 promote leukemogenesis and why children with Down syndrome (DS) (ie, trisomy 21) are particularly at risk leukemia development. Here, we propose that RUNX1 isoform disequilibrium RUNX1A bias key to DS-associated myeloid (ML-DS). Starting Hsa21-focused CRISPR–CRISPR-associated protein 9 screens, uncovered a strong specific...
Obesity is associated with chronic low-grade inflammation of adipose tissue (AT) and an increase AT macrophages (ATMs) that linked to the onset type 2 diabetes. We have recently shown neutralization interleukin (IL)-6 in obese organ cultures inhibits proliferation ATMs, which occurs preferentially alternatively activated macrophage phenotype. In this study, we investigated biology metabolic phenotype mice myeloid cell-specific IL-6Rα deficiency (Il6ra Δmyel) after normal chow 20 weeks...
Oral squamous cell carcinoma (OSCC), a major subgroup of head and neck (HNSCC), is an aggressive disease that preferentially spreads to cervical lymph nodes. Positive node status important predictor survival in OSCC [1-3]. Hence, better understanding the molecular mechanisms underlying oral cancer metastasis identification therapeutic vulnerabilities are needed prevent treat metastatic disease. We collected 87 primary tumors 21 (LNM) from 72 patients conduct comprehensive transcriptome-wide...
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...
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...
Down-regulation of adherens junctions is a frequent event in carcinogenesis. How desmosomal proteins contribute to tumor formation by regulating the balance between adhesion and proliferation not well understood. The protein plakophilin 1 can increase intercellular recruiting plasma membrane or stimulate enhancing translation rates. Here, we show that these dual functions are regulated growth factor signaling. Insulin stimulation induced phosphorylation 1, which correlated with reduced an...
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...
White adipose tissue (WAT) fibrosis, characterized by an excess of extracellular (ECM) matrix components, is strongly associated with WAT inflammation and dysfunction due to obesity. Interleukin (IL)-13 IL-4 were recently identified as critical mediators in the pathogenesis fibrotic diseases. However, their role fibrosis still ill-defined. We therefore established ex vivo organotypic culture system demonstrated upregulation fibrosis-related genes increase α-smooth muscle actin (αSMA)...
Abstract Plakophilin 4 (PKP4) is a component of cell–cell junctions that regulates intercellular adhesion and Rho-signaling during cytokinesis with an unknown function epidermal differentiation. Here we show keratinocytes lacking PKP4 fail to develop cortical actin ring, preventing adherens junction maturation generation tissue tension. Instead, PKP4-depleted cells display increased stress fibers. PKP4-dependent RhoA localization at AJs was required activate RhoA-ROCK2-MLCK-MLC2 axis...
Abstract Naturally occurring circular RNAs efficiently impair miRNA functions. Synthetic may thus serve as potent agents for inhibition. Their therapeutic effect critically relies on (i) the identification of optimal targets, (ii) optimization decoy structures and (iii) development efficient formulations their use drugs. In this study, we extensively explored functional relevance miR-21-5p in cancer cells. Analyses transcriptomes reveal that is by far most abundant human cancers. Deletion...
Pancreatic adenocarcinoma (PDAC) is one of the major causes cancer-associated deaths worldwide, with a dismal prognosis that has not significantly changed over last decades. Transcriptional analysis provided valuable insights into pancreatic tumorigenesis. Specifically, cancer subtypes were identified, characterized by specific mutations and gene expression changes associated differences in patient survival. In addition to differentially regulated mRNAs, non-coding RNAs, including long RNAs...
Abstract The RAVER1 protein serves as a co-factor in guiding the polypyrimidine tract-binding (PTBP)-dependent control of alternative splicing (AS). Whether solely acts concert with PTBPs and how it affects cancer cell fate remained elusive. Here, we provide first comprehensive investigation RAVER1-controlled AS models. This reveals pro-oncogenic role modulating tumor growth epithelial-mesenchymal-transition (EMT). Splicing analyses protein-association studies indicate that guides...
Pancreatic ductal adenocarcinomas (PDAC) belong to the most frequent and deadly malignancies in western world. Mutations KRAS TP53 along with some other polymorphisms occur almost universally are likely be responsible for tumor initiation. However, these mutations cannot explain heterogeneity therapeutic responses observed PDAC patients, which limits efficiency of current strategies. Instead, recent classifications samples based on transcriptomics data thus include information about...
Abstract T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-refractory malignancy with limited therapeutic options and poor prognosis. Current disease concepts implicate TCL1A oncogene-mediated enhanced receptor (TCR) signaling aberrant DNA repair as central perturbed pathways. We discovered that recurrent gains on chromosome 8q more frequently involve the argonaute RISC catalytic component 2 (AGO2) gene than adjacent MYC locus affected minimally amplified genomic region. AGO2 has been...