miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma

Marissa Williams, Michaela B. Kirschner, Yuen Yee Cheng, Jacky Hanh, Jocelyn Weiss, Nancy Mugridge, Casey M. Wright, Anthony Linton, Steven C. Kao, J. James B. Edelman, Michael P. Vallely, Brian C. McCaughan, Wendy Cooper, Sonja Klebe, Ruby C. Y. Lin, Himanshu Brahmbhatt, Jennifer MacDiarmid, Nico van Zandwijk, Glen Reid

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    55 Citations (Scopus)
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    Abstract

    Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displays characteristic alterations in microRNA expression. Recently it was reported that the expression of a subset of microRNAs can distinguish between MPM and adenocarcinoma of the lung. However, the functional importance of these changes has yet to be investigated. We compared expression of miR-192, miR-193a-3p and the miR-200 family in normal pleura and MPM tumor specimens and found a statistically significant reduction in the levels of miR-193a-3p (3.1-fold) and miR-192 (2.8-fold) in MPM. Transfection of MPM cells with a miR-193a-3p mimic resulted in inhibition of growth and an induction of apoptosis and necrosis in vitro. The growth inhibitory effects of miR-193a-3p were associated with a decrease in MCL1 expression and were recapitulated by RNAi-mediated MCL1 silencing. Targeted delivery of miR-193a-3p mimic using EDV minicells inhibited MPM xenograft tumour growth, and was associated with increased apoptosis. In conclusion, miR-193a-3p appears to have importance in the biology of MPM and may represent a target for therapeutic intervention.
    Original languageEnglish
    Pages (from-to)23480-23495
    Number of pages16
    JournalOncotarget
    Volume6
    Issue number27
    DOIs
    Publication statusPublished - 2015

    Bibliographical note

    Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

    Keywords

    • tumor suppressor
    • mesothelioma
    • microRNA
    • miR-193a

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