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    MiRNA-29a regulates the expression of numerous proteins and reduces the invasiveness and proliferation of human carcinoma cell lines


    Muniyappa, M.K. and Dowling, Paul and Henry, M. and Meleady, Paula and Doolan, P. and Gammell, P. and Clynes, Martin and Barron, N. (2009) MiRNA-29a regulates the expression of numerous proteins and reduces the invasiveness and proliferation of human carcinoma cell lines. European Journal of Cancer, 45 (17). pp. 3104-3118. ISSN 0959-8049

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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 30 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.

    Item Type: Article
    Keywords: In vitro invasion; microRNA; Proteomic profiling; Lung cancer; miR-29a;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7346
    Identification Number: https://doi.org/10.1016/j.ejca.2009.09.014
    Depositing User: Paul Dowling
    Date Deposited: 16 Aug 2016 15:47
    Journal or Publication Title: European Journal of Cancer
    Publisher: Elsevier
    Refereed: Yes
    Funders: Higher Education Authority (HEA), Science Foundation Ireland (SFI)
    URI:

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