Niall Barron

Publications (54) View all

• Article: The human L1 element: a potential biomarker in cancer prognosis, current status and future directions.

  O Piskareva, W Lackington, D Lemass, C Hendrick, P Doolan, N Barron
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  ABSTRACT: The discovery of new biomarkers is a rapidly advancing area in cancer biology. The challenge of biomarker development for broad clinical use requires the translation of lab-based knowledge into clinical practice. The Long Interspersed Nuclear Elements-1 (LINE-1s or L1 elements) are active members of an autonomous family of non-LTR retrotransposons and occupy nearly 17% of the human genome. There is strong experimental evidence that the global hypomethylation of genomic DNA in cancer cells results in the activation of L1s and their expression is detectable at genome, transcriptome and proteome levels in human cancer cells. Thus, human L1s constitute a potential marker for cancer cells. In this review we have attempted to scrutinize L1 expression profiles in clinical cancer studies by undertaking a comprehensive systematic analysis of papers published in the field so far with a view to providing a more complete picture of the detection methods used, improvements achieved and potential future directions. Ultimately, we will try to evaluate the potential of L1s as a molecular marker in cancer detection.
  Current Molecular Medicine 06/2011; 11(4):286-303. · 5.10 Impact Factor
• Article: Engineering CHO cell growth and recombinant protein productivity by overexpression of miR-7.

  N Barron, N Kumar, N Sanchez, P Doolan, C Clarke, P Meleady, F O'Sullivan, M Clynes
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  ABSTRACT: The efficient production of recombinant proteins by Chinese Hamster Ovary (CHO) cells in modern bioprocesses is often augmented by the use of proliferation control strategies. The most common method is to shift the culture temperature from 37 °C to 28-33 °C though genetic approaches to achieving the same effect are also of interest. In this work we used qRT-PCR-based expression profiling using TLDA™ cards to identify miRNAs displaying differential expression 24h after temperature-shift (TS) from 37 °C to 31 °C. Six miRNAs were found to be significantly up-regulated (mir-219, mir-518d, mir-126, mir-30e, mir-489 and mir-345) and four down-regulated (mir-7, mir-320, mir-101 and mir-199). Furthermore, qRT-PCR analysis of miR-7 expression over a 6 day batch culture, with and without TS, demonstrated decreased expression over time in both cultures but to a significantly greater extent in cells shifted to a lower culture temperature. Unexpectedly, when miR-7 levels were increased transiently by transfection with miR-7 mimic in CHO-K1 cells, cell proliferation at 37 °C was effectively blocked over a 96 h culture period. On the other hand, transient inhibition of endogenous miR-7 levels using antagonists had no impact on cell growth. The exogenous overexpression of miR-7 also resulted in increased normalised (per cell) production at 37 °C, though the yield was lower than cells grown at reduced temperature. This is the first report demonstrating a functional impact of specific miRNA disregulation on CHO cell behavior in batch culture and provides some evidence of the potential which these molecules may have in terms of engineering targets in CHO production clones. Finally, we report the cloning and sequencing of the hamster-specific cgr-miR-7.
  Journal of biotechnology 01/2011; 151(2):204-11. · 2.88 Impact Factor
• Article: Interaction of Plasma Deposited HMDSO-Based Coatings with Fibrinogen and Human Blood Plasma: The Correlation between Bulk Plasma, Surface Characteristics and Biomolecule Interaction

  RP GANDHIRAMAN, MK MUNIYAPPA, M DUDEK, C COYLE, C VOLCKE, AJ KILLARD, P BURHAM, S DANIELS, N BARRON, M CLYNES, DC CAMERON
  Plasma Processes and Polymers 01/2010; 7(5):411-421. · 2.47 Impact Factor
• Article: MiRNA-29a regulates the expression of numerous proteins and reduces the invasiveness and proliferation of human carcinoma cell lines.

  M K Muniyappa, P Dowling, M Henry, P Meleady, P Doolan, P Gammell, M Clynes, N Barron
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  ABSTRACT: In this study we have identified a functional role for miR-29a in cancer cell invasion and proliferation. MiRNA expression profiling of human NSCLC cell lines indicated that miR-29a levels were reduced in more invasive cell lines. Exogenous overexpression of miR-29a in both lung and pancreatic cancer cell lines resulted in a significant reduction in the invasion phenotype, as well as in proliferation. 2D DIGE proteomic profiling of cells transfected with pre-miR-29a or anti-miR-29a resulted in the identification of over 100 differentially regulated proteins. The fold change of protein expression was generally modest--in the range 1.2-1.7-fold. Only 14 were predicted computationally to have miR-29a seed sequences in their 3' UTR region. Subsequent studies using siRNA to knock down several candidate proteins from the 2D DIGE experiment identified RAN (a member of the RAS oncogene family) which significantly reduced the invasive capability of a model lung cancer cell line. We conclude that miR-29a has a significant anti-invasive and anti-proliferative effect on lung cancer cells in vitro and functions as an anti-oncomir. This function is likely mediated through the post-transcriptional fine tuning of the cellular levels of several proteins, both directly and indirectly, and in particular we provide some evidence that RAN represents one of these.
  European journal of cancer (Oxford, England: 1990) 10/2009; 45(17):3104-18. · 4.12 Impact Factor
• Article: Transcriptomic analysis of clonal growth rate variation during CHO cell line development.

  Padraig Doolan, Colin Clarke, Paula Kinsella, Laura Breen, Paula Meleady, Mark Leonard, Lin Zhang, Martin Clynes, Sinead Aherne, Niall Barron
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  ABSTRACT: The selection of clones displaying a high rate of cell growth is an essential component of Chinese hamster ovary (CHO) cell line development. In recent years various "omics" technologies have been utilised to understand the mechanisms underlying bioprocess phenotypes. In this study, gene expression analysis using a CHO-specific microarray was conducted for a panel of CHO-K1 MAb-secreting cell lines spanning a range of growth rates that were derived from a single cell line development project. In-silico functional analysis of the resulting transcriptomic data revealed the overrepresentation of biological processes such as cell cycle and translation within those genes upregulated during fast growth, while genes associated with cellular homeostasis were downregulated. Using differential expression and correlation analysis we identified a high priority group of 416 transcripts (190 upregulated; 226 downregulated) associated with growth rate. Expression changes of eight of these genes were independently confirmed by qPCR. Finally, we demonstrate the enrichment of predicted mRNA targets of miR17-92, a microRNA (miRNA) cluster known to be upregulated during rapid proliferation, within downregulated transcripts.
  Journal of biotechnology 05/2013; · 2.88 Impact Factor