A5042431725- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- RNA Research and Splicing
- Pancreatic and Hepatic Oncology Research
- Circular RNAs in diseases
- Cancer Genomics and Diagnostics
- Extracellular vesicles in disease
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Kruppel-like factors research
- Sphingolipid Metabolism and Signaling
- Estrogen and related hormone effects
- Fibroblast Growth Factor Research
- Cancer Cells and Metastasis
- Molecular Biology Techniques and Applications
- Neuroendocrine Tumor Research Advances
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Cytokine Signaling Pathways and Interactions
- Gastrointestinal Tumor Research and Treatment
- RNA Interference and Gene Delivery
- Protein Tyrosine Phosphatases
- Renal and related cancers
- Cancer Mechanisms and Therapy
- Advanced biosensing and bioanalysis techniques
University of Sussex
2018-2025
Imperial College London
2015-2024
Hammersmith Hospital
2010-2019
The London College
2012-2019
Medical University of Silesia
2016
Imperial College Healthcare NHS Trust
2012-2013
University of East Anglia
2013
Charing Cross Hospital
2012-2013
Center for Translational Molecular Medicine
2013
Cancer Research UK
2013
Following estrogenic activation, the estrogen receptor-α (ERα) directly regulates transcription of target genes via DNA binding. MicroRNAs (miRNAs) modulated by ERα have potential to fine tune these regulatory systems and also provide an alternate mechanism that could impact on estrogen-dependent developmental pathological systems. Through a microarray approach, we identify subset microRNAs ERα, which include upregulation miRNAs derived from processing paralogous primary transcripts (pri-)...
We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. report that the majority of genes encode mature isomers vary in size by one or more bases at 3′ and/or 5′ end miRNA. Northern blotting for individual miRNAs showed proportions isomiRs expressed a single gene often differ between cell tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins vivo active luciferase assays, indicating they are functional. Bioinformatics...
Drugs that inhibit estrogen receptor-α (ER) activity have been highly successful in treating and reducing breast cancer progression ER-positive disease. However, resistance to these therapies presents a major clinical problem. Recent genetic studies shown mutations the ER gene are found >20% of tumours progress on endocrine therapies. Remarkably, great majority localize just few amino acids within or near critical helix 12 region hormone binding domain, where they likely be single allele...
Background MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these not compared with pre-malignant tumors. We wished to compare the miRNA signatures benign cystic tumors (BCT) of low and high malignant potential PDAC, order identify miRNAs deregulated during PDAC development. The mechanistic consequences dysregulation were further evaluated. Methods Tissue samples obtained at a tertiary unit from individuals BCT PDAC. MiRNA profiling was...
Glypican-1 (GPC1) is expressed in pancreatic ductal adenocarcinoma (PDAC) cells and adjacent stromal fibroblasts. Recently, GPC1 circulating exosomes (crExos) have been shown to be able detect early stages of PDAC. In this study, we investigated the usefulness crExos as a biomarker for PDAC.Plasma was obtained from patients with benign disease (n = 16) PDAC 27) prior pancreatectomy, were isolated by ultra-centrifugation. Protein extracted surgical specimens (adjacent normal pancreas, n 13;...
Abstract Endocrine therapies target the activation of oestrogen receptor alpha (ERα) via distinct mechanisms, but it is not clear whether breast cancer cells can adapt to treatment using drug-specific mechanisms. Here we demonstrate that resistance emerges epigenetic reprogramming. Resistant display a spectrum phenotypical changes with invasive phenotypes evolving in lines resistant aromatase inhibitor (AI). Orthogonal genomics analysis reprogrammed regulatory regions identifies individual...
TGF-β/Activin induces epithelial-to-mesenchymal transition and stemness in pancreatic ductal adenocarcinoma (PDAC). However, the microRNAs (miRNAs) regulated during this response have remained yet undetermined. Here, we show that TGF-β transcriptionally MIR100HG lncRNA, containing miR-100, miR-125b let-7a its intron, via SMAD2/3. Interestingly, find although pro-tumourigenic miR-100 accordingly increase, amount of anti-tumourigenic is unchanged, as also LIN28B inhibiting maturation. Notably,...
Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development ultimately metastasis. A number of studies have implicated microRNAs in the regulation cancer invasion migration. Here, we show that miR-23b regulates focal adhesion, spreading, cell-cell junctions formation lamellipodia breast (BC), implicating a central role it dynamics. Inhibition miR-23b, using specific sponge construct, leads to an increase migration metastatic spread vivo, indicating as...
Similar to healthy tissues, many blood and solid malignancies are now thought be organised hierarchically, with a subset of stem-like cancer cells that self-renew while giving rise more differentiated progeny. Understanding targeting these stem in breast cancer, which may possess enhanced chemo- radio-resistance compared the non-stem tumor bulk, has become an important research area. Markers including CD44, CD24, ALDH activity can assessed using fluorescence activated cell sorting (FACS)...
MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression. They characterized by specific maturation processes defined canonical and non-canonical biogenic pathways. Analysis of ∼0.5 billion sequences from mouse data sets derived different tissues, developmental stages cell types, partly either ablation or mutation the main proteins belonging to miRNA processor complexes, reveals 66 high-confidence new genomic loci coding for miRNAs could be processed in a manner. A proportion...
Abstract The use of anthracyclines such as doxorubicin (DOX) has improved outcome in cancer patients, yet associated risks cardiomyopathy have limited their clinical application. DOX-associated cardiotoxicity is frequently irreversible and typically progresses to heart failure (HF) but our understanding molecular mechanisms underlying this essential for development cardioprotective strategies remains largely obscure. As microRNAs (miRNAs) been shown play potent regulatory roles both...
Article10 February 2016Open Access Transparent process miR-515-5p controls cancer cell migration through MARK4 regulation Olivier E Pardo Corresponding Author Department of Surgery & Cancer, Division Imperial Centre for Translational and Experimental Medicine (ICTEM), College, Hammersmith Hospital Campus, London, UK Search more papers by this author Leandro Castellano Catriona Munro Yili Hu Oncology, College Healthcare NHS Trust, Charing Cross Hospital, Francesco Mauri Jonathan Krell Romain...
Circulating tumor cells (CTCs) disseminate from the primary and travel through bloodstream lymphatic system. The detection of and/or increase in number CTCs during a patient’s clinical course may be harbinger forthcoming overt metastasis. We aimed to examine impact 2 different surgical techniques, standard (ST) pancreaticoduodenectomy (PD) no-touch isolation (NT) PD, on behavior outcome patients with pancreatic cancer by using as biomarkers. In this pilot study, were randomized either ST-PD...
Sphingosine kinase 1 (SK1) plays an important role in estrogen-dependent breast tumorigenesis, but its regulation is poorly understood. A subset of microRNAs (miRNA, miR) regulated by estrogen and contributes to cellular proliferation cancer progression. Here, we describe that miR-515-5p transcriptionally repressed receptor α (ERα) functions as a tumor suppressor cancer. Its downregulation enhances cell SK1 activity, mediated reduction posttranscriptional repression. Enforced expression...
Background The growth arrest-specific transcript 5 gene (GAS5) encodes a long noncoding RNA (lncRNA) and hosts number of small nucleolar RNAs (snoRNAs) that have recently been implicated in multiple cellular processes cancer. Here, we investigate the relationship between DNA damage, p53, GAS5 snoRNAs to gain further insight into potential role this locus cell survival oncogenesis both vivo vitro. Methods We used quantitative techniques analyse effect damage on snoRNA expression assess p53...
Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response. In this study, we aimed profile the global miRNome of SBNETs, identify microRNAs (miRNAs) involved tumour progression for use as potential biomarkers. Two independent miRNA profiling experiments were performed ( n =90), including primary SBNETs =28), adjacent normal (NSB; =14), matched lymph node (LN) metastases =24), LNs =7), liver =2)...
AbstractOnly a subset of radically-resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from gemcitabine-based chemotherapy, thus the identification novel prognostic factors is essential. In high-throughput, microRNA (miRNA) array, miR-211 emerged as best discriminating miRNA, with high expression associated long survival. Here, we further explored biological role miRNA-211 in gemcitabine activity human PDAC cells (SUIT-2) subclones SUIT2-007 and SUIT2-028. Our results showed...